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Thermosensitive and osmoreceptive afferent fibers in the hepatic branch of the vagus nerve
Journal of the Autonomic Nervous System, 10 (1984) 269-273
269
Elsevier JAN 00350
Thermosensitive and osmoreceptive afferent fibers in the hepatic branch of the vagus nerve A. A d a c h i Department of Physiology, Okayama University Dental School, Shikata- cho Okayama- 700 (Japan)
(ReceivedSeptember20th, 1983) (Accepted February 10th, 1984)
Key words: vagus -
hepatic afferent nerve hepatic osmoreceptor
thermosensitive afferent nerve -
Abstract
The hepatic vagus nerve contains various thermosensitive afferent fibers which are widely varied in their sensitivity. Their Q10 values lie between 4 and 16. The discharge rate is positively correlated with increase of liver temperature (warm fiber type). The result supports the existence of a thermosensitive structure in the liver which may possibly contribute to maintain thermal homeostasis. Neural responses to the osmotic changes in the perfusion solution have been analyzed. It was found that two different types of osmosensitive afferent fibers exist in the hepatic vagus; one is characterized by increasing the frequency of spike discharges in response to higher osmotic pressure, while the other shows the same response to lowered levels. Behavioral changes caused by hepatic vagotomy were observed. These results provide evidence for the existence of an osmoreceptor mechanism. The role of these hepatic afferent nerves in homeostasis are briefly discussed.
Introduction
As reviewed by Sawchenko and Friedman [19], evidence of various sensory receptors within the liver has grown in abundance recently. It is assumed that these Correspondence: A. Adachi, Dept. of Physiology, Okayama University Dental School, Shikata-cho Okayama-700, Japan.
0165-1838/84/$03.00 © 1984 ElsevierSciencePublishers B.V.
270 sensory receptors such as osmo-, baro-, metabolic and other miscellaneous receptors may play an important role in maintaining homeostasis in mammals. This short review briefly summarizes functions of thermosensitive and osmoreceptive afferent nerves which innervate the liver as well as evidence in support of their existence.
T h e r m o s e n s i t i v e afferent nerve in the hepatic vagus
It has been extensively studied and demonstrated that many thermoreceptors are distributed not only in the skin and mucosa [6,12,13,25] but within the hypothalamus [15] and the spinal cord [21]. These detect temperature changes in the external as well as the internal environment and in turn induce regulatory reflexes that maintain thermal homeostasis. Some evidence suggests that thermoreceptors might possibly exist in arteries, veins [10,24] and in the abdomen [3,17,18] which are traditionally not considered as locations of these receptors. Furthermore. a possible thermoreceptive mechanism in the hepatoportal region may be proposed in relation to the specific dynamic action which is attributable to suppression of food intake. Adachi and Niijima [2] were the first to report that the hepatic branch of the vagus includes thermosensitive afferent fibers which are responsive to slight increases in the liver temperature. Guinea-pigs were used as subjects. Under urethane anesthesia, the liver was excised from the animal and perfused with Ringer-Lock solution. Thermal stimulation of the liver was applied by increasing the temperature of the perfusate by means of a thermomodule inserted into the perfusion circuit. The hepatic branch of the vagus was dissected into a fine filament and the neural activity was recorded by means Of conventional electrophysiological equipment. As shown in Fig. 1, a fine nerve filament is markedly responsive to increases in the liver temperature. Thirteen filaments out of a total of 57 were responsive to thermal stimulation and their Q10 values lay between 4 and 16. Since no response was elicited in these thermosensitive elements by mechanical stimulation, it excludes the possibility that mechanoreceptors respond secondarily to swelling caused by warming the liver. The thermal specificity of these afferent fibers is also indicated by the fact that the hepatic osmosensitive fibers are insensitive to thermal stimulation applied to the
0 *C
37 I
I
5 NIN Fig, 1. Simultaneous recording of afferent discharge rates from the hepatic branch of vagus (upper trace) and liver temperature (lower trace).
271 liver. In this paper, no discussion is devoted to a role of this afferent system on the control of food intake, because clarification of this problem had not been the purpose of this study. Thermostatic regulation of food intake has been proposed by Brobeck and his colleagues [7,22]. They tried to establish this hypothesis in a number of ways. On the contrary, Kennedy has advanced a number of arguments against them [14]. One of Kennedy's arguments is that the hypothalamic thermoreceptive neuron cannot discriminate between temperature increase caused by the specific dynamic action and that produced by muscular contraction. The hepatic thermosensitive afferent fiber may serve to distinguish between the heat production of the liver and that of the muscles. However, no effect on feeding behavior was recognized as a result of section of the hepatic branch of the vagus [1]. Other thermosensitive structures in the abdomen might also be involved in this mechanism. Tarozzi et al. have postulated the possibility of a hepatic thermoreceptive mechanism based on the results obtained by their behavioral experiments [9,23]. When the liver surface was locally heated by 0.5-1° C, the fasted rats consumed less food than the control fasted rats. No effect on feeding was observed when other abdominal regions were heated. During hepatic heating, rats devoted a significantly longer period to masticatory movement but not to feeding behavior. This is an important observation since it again emphasizes involvement of the hepatic thermosensitive afferent fibers in the regulation of food intake. Thus, it is likely that the thermostatic regulation may be partially involved in the short-term regulation of feeding though it cannot be the only regulatory mechanism as pointed out by Anand [4].
Hepatic osmoreceptor mechanism Existence of an osmoreceptor mechanism in the hepatoportal system was first suggested by Haberich and his colleagues on the basis of the fact that very small amounts of water or hypertonic saline infused into the portal vein produce diuresis or antidiuresis in the rats and that these effects can be abolished by cutting the hepatic branch of the vagus [8,11]. However, Schneider et al. [20] carried out an experiment similar to that of Haberich in conscious dogs and failed to provide evidence for an osmoreceptor mechanism in the liver. The contradictory results of Haberich and Schneider et al. suggest a species difference in hepatic osmoreception. It is likely that there is a species difference particularly in regulatory mechanism of water balance between animals which live by a river and in a desert, possibly between a herbivore, a carnivore and an omnivore. In case of disagreements, discussions should be confined to consideration of the same species. No electrophysiological evidence had been reported until that resulting from the preliminary work on the guinea-pigs by Niijima [16]. He presented neurophysiological evidence suggesting that there are osmoreceptors in the liver of the guinea pig. This hepatic osmoreceptor was affected by mannose, glucose and sucrose as well as by NaC1. These results are at variance with those reported by Andrews and Orbach
272
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130
140
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Fig. 2. Solid circles show that responses of one type of fiber are positivelycorrelated with increases in osmotarity; open circles show that responses of another type of fiber are correlated with decreases in osmolarity. Ordinate: percent of base-line discharge rate. Abscissa: concentrations of NaCI in mM contained in test solutions. [5] who suggested that only a sodium receptor, not a true osmoreceptor, was involved in production of discharge in the hepatic vagus of the rabbit. Thus, Adachi et al. [1] confirmed that osmoreceptive afferent fibers exist in the hepatic branch of the vagus in the rat. In these studies also behavioral techniques were used to ascertain the physiological meaning of such an afferent system on the regulation of water balance. The rat liver was perfused with Ringer solution through the portal vein by use of a perfusion system which was designed to switch from standard Ringer solution to hypertonic or hypotonic Ringer solution. Neural responses to the osmotic changes m the perfusion solutions were analyzed. They showed that two dlffrent types of osmosensitive afferent fibers exist in the hepatic vagus; one increases the diseha~e rate in response to higher osmotic pressure, while the other shows a similar response to lower osmotic pressure (Fig. 2). Behavioral chanses caused by hepatic vagotomy were observed. Though no d i f f e i ~ c e s could be detected in routine behavior (e.g. daily intakes of food and water, body weight increase) between the vagotomized and the sham-operated rats, the former lost the ability to adjust urine concentration immediately in response to osmotic changes in the internal environment. It is concluded that a hepatic osmoreceptor mechanism exists in the rats and transmits the signals to the central nervous system via the vagus. However, there is no reason for concluding that this mechar.lsm plays a predominant role in isoosmotic regulation or dominates all other systems which detect osmotic change.
Ad,mwlHIllamS The author wishes to thank Miss K ~ ~ a t a for t~ing: Lhe ma.-lu~ript. This work was s u ~ e d by a research grant f r ~ ~ Japanese ~ $ ~ of ~tion,
273
References 1 Adachi, A., Niijima, A. and Jacobs, H.L., An hepatic osmoreceptor mechanism in the rat: electrophysiological and behavioral studies, Amer. J. Physiol., 231 (1976) 1043-1049. 2 Adachi, A. and Niijima, A., Thermosensitive afferent fibers in the hepatic branch of the vagus nerve in the guinea pig, J. auton. Nerv. System., 5 (1982) 101-109. 3 Adair, E.R., Evaluation of some controller inputs to behavioral temperature regulation, Int. J. Biometeoroi., 15 (1971) 121-128. 4 Anand, B.K., Nervous regulation of food intake, Physiol. Rev., 41 (1961) 677-708. 5 Andrews, W.H.H. and Orbach, J., Sodium receptors activating some nerves of perfused rabbit livers, Amer. J. Physiol., 227 (1974) 1273-1275. 6 Boman, K.K.A. and Hensel, H., Afferent impulses in cutaneous sensory nerves in conscious human subjects, J. Neurophysiol., 193 (1960) 564-578. 7 Brobeck, J.R., Food intake as mechanism of temperature regulation, Yale J. Biol. Med., 20 (1948) 545-552. 8 Dennhardt, R., Ohm, W.W. and Haberich, F.J., Die Ausschaltung der Leber~te des N. vagus an der wachen Ratte und ihr Einfluss auf die hepatogene Diurese-indirekter Beweis fi~r die afferente Leitung der Leber-Osmoreceptoren i~ber den N. vagus, Pfli~ger's Arch. ges. Physiol., 328 (1971) 51-56. 9 DiBella, L. and Tarozzi, G., Probable liver thermoreceptors as modulators of food and water intake (Abstr.), Int. Congr. Physiol. Sci. 26th Jerusalem Satellite Symp., 1974. 10 Downey, J.A., Mattram, R.F. and Picketing, G.W., The location by regional cooling of central temperature receptors in the conscious rabbit, J. Physiol. (Lond.), 170 (1964) 415-441. 11 Habetich, F.J., Osmoreception in the portal circulation, Fed. Proc., 27 (1968) 1137-1141. 12 Hensel, H., Iggo, A. and Witt, I., A quantitative study of sensitive cutaneous thermoreceptors with C afferent fibers, J. Physiol. (Lond.), 153 (1960) 113-126. 13 lggo, A., Cutaneous thermoreceptors in primates and sub-primates, J. Physiol. (Lond.), 200 (1969) 403-430. 14 Kennedy, G.C., Role of depot fat in hypothalamic control of food intake in rat, Proc. roy. Soc. B, 140 (1953) 578-592. 15 Nakayama, T., Hammei, H.T., Hardy, J.D. and Eisenman, J.S., Thermal stimulation of electrical activity of single units of preoptic region, Amer. J. Physiol., 204 (1963) 1122-1126. 16 Niijima, A., Afferent discharges from osmoreceptors in the liver of the guinea pig, Science, 166 (1969) 1519-1520. 17 Rawson, R.D., Thermoregulatory responses to intra-abdominal heating in sheep, Physiologist, 12 (1969) 337. 18 Riedel, W., Siaplauras, G. and Simon, E., Intra-abdominal thermosensitivity in the rabbit as compared with spinal thermosensitivity, Pfliiger's Arch. ges., Physiol., 340 (1973) 59-70. 19 Sawchenko, P.E. and Friedman, M.I., Sensory functions of the liver-a review, Amer. J. Physiol., 236 (1979) R5-R20. 20 Schneider, E.G., Davis, J.O., Robb, C.A., Baumber, J.S., Johnson, J.A. and Wright, F.S., Lack of evidence for a hepatic osmoreceptor mechanism in conscious dogs, Amer. J. Physiol., 218 (1970) 42-45. 21 Simon, E., Rautenberg, W., Thauer, R. and Itiki, M., AusliSsung thermoregulatorischer Reaktion dutch lokale Kiahlung im Vertebralkanal, Naturwissenschaften, 50 (1963) 337. 22 Strominger, J.L. and Brobeck, J.R., Mechanism of regulation of food intake, Yale J. Biol. Med., 25 (1953) 383-390. 23 Trazzi, G., DiBeila, L., Scalera, G. and Rossi, M.T., Role of proprioceptive masticatory feedback in the rat feeding pattern behavior, Nutr. Metab., 21 Suppl. 1 (1977) 70-72. 24 Thompson, F.J. and Barnes, C.D., Evidence for thermosensitive elements in the femoral vein, Life Sci., 91 (1970) 309-312. 25 Zotterman, Y., Specific actionpotentials in lingual nerve of cat, Scand. Arch. Physiol., 75 (1936) 105-120.
269
Elsevier JAN 00350
Thermosensitive and osmoreceptive afferent fibers in the hepatic branch of the vagus nerve A. A d a c h i Department of Physiology, Okayama University Dental School, Shikata- cho Okayama- 700 (Japan)
(ReceivedSeptember20th, 1983) (Accepted February 10th, 1984)
Key words: vagus -
hepatic afferent nerve hepatic osmoreceptor
thermosensitive afferent nerve -
Abstract
The hepatic vagus nerve contains various thermosensitive afferent fibers which are widely varied in their sensitivity. Their Q10 values lie between 4 and 16. The discharge rate is positively correlated with increase of liver temperature (warm fiber type). The result supports the existence of a thermosensitive structure in the liver which may possibly contribute to maintain thermal homeostasis. Neural responses to the osmotic changes in the perfusion solution have been analyzed. It was found that two different types of osmosensitive afferent fibers exist in the hepatic vagus; one is characterized by increasing the frequency of spike discharges in response to higher osmotic pressure, while the other shows the same response to lowered levels. Behavioral changes caused by hepatic vagotomy were observed. These results provide evidence for the existence of an osmoreceptor mechanism. The role of these hepatic afferent nerves in homeostasis are briefly discussed.
Introduction
As reviewed by Sawchenko and Friedman [19], evidence of various sensory receptors within the liver has grown in abundance recently. It is assumed that these Correspondence: A. Adachi, Dept. of Physiology, Okayama University Dental School, Shikata-cho Okayama-700, Japan.
0165-1838/84/$03.00 © 1984 ElsevierSciencePublishers B.V.
270 sensory receptors such as osmo-, baro-, metabolic and other miscellaneous receptors may play an important role in maintaining homeostasis in mammals. This short review briefly summarizes functions of thermosensitive and osmoreceptive afferent nerves which innervate the liver as well as evidence in support of their existence.
T h e r m o s e n s i t i v e afferent nerve in the hepatic vagus
It has been extensively studied and demonstrated that many thermoreceptors are distributed not only in the skin and mucosa [6,12,13,25] but within the hypothalamus [15] and the spinal cord [21]. These detect temperature changes in the external as well as the internal environment and in turn induce regulatory reflexes that maintain thermal homeostasis. Some evidence suggests that thermoreceptors might possibly exist in arteries, veins [10,24] and in the abdomen [3,17,18] which are traditionally not considered as locations of these receptors. Furthermore. a possible thermoreceptive mechanism in the hepatoportal region may be proposed in relation to the specific dynamic action which is attributable to suppression of food intake. Adachi and Niijima [2] were the first to report that the hepatic branch of the vagus includes thermosensitive afferent fibers which are responsive to slight increases in the liver temperature. Guinea-pigs were used as subjects. Under urethane anesthesia, the liver was excised from the animal and perfused with Ringer-Lock solution. Thermal stimulation of the liver was applied by increasing the temperature of the perfusate by means of a thermomodule inserted into the perfusion circuit. The hepatic branch of the vagus was dissected into a fine filament and the neural activity was recorded by means Of conventional electrophysiological equipment. As shown in Fig. 1, a fine nerve filament is markedly responsive to increases in the liver temperature. Thirteen filaments out of a total of 57 were responsive to thermal stimulation and their Q10 values lay between 4 and 16. Since no response was elicited in these thermosensitive elements by mechanical stimulation, it excludes the possibility that mechanoreceptors respond secondarily to swelling caused by warming the liver. The thermal specificity of these afferent fibers is also indicated by the fact that the hepatic osmosensitive fibers are insensitive to thermal stimulation applied to the
0 *C
37 I
I
5 NIN Fig, 1. Simultaneous recording of afferent discharge rates from the hepatic branch of vagus (upper trace) and liver temperature (lower trace).
271 liver. In this paper, no discussion is devoted to a role of this afferent system on the control of food intake, because clarification of this problem had not been the purpose of this study. Thermostatic regulation of food intake has been proposed by Brobeck and his colleagues [7,22]. They tried to establish this hypothesis in a number of ways. On the contrary, Kennedy has advanced a number of arguments against them [14]. One of Kennedy's arguments is that the hypothalamic thermoreceptive neuron cannot discriminate between temperature increase caused by the specific dynamic action and that produced by muscular contraction. The hepatic thermosensitive afferent fiber may serve to distinguish between the heat production of the liver and that of the muscles. However, no effect on feeding behavior was recognized as a result of section of the hepatic branch of the vagus [1]. Other thermosensitive structures in the abdomen might also be involved in this mechanism. Tarozzi et al. have postulated the possibility of a hepatic thermoreceptive mechanism based on the results obtained by their behavioral experiments [9,23]. When the liver surface was locally heated by 0.5-1° C, the fasted rats consumed less food than the control fasted rats. No effect on feeding was observed when other abdominal regions were heated. During hepatic heating, rats devoted a significantly longer period to masticatory movement but not to feeding behavior. This is an important observation since it again emphasizes involvement of the hepatic thermosensitive afferent fibers in the regulation of food intake. Thus, it is likely that the thermostatic regulation may be partially involved in the short-term regulation of feeding though it cannot be the only regulatory mechanism as pointed out by Anand [4].
Hepatic osmoreceptor mechanism Existence of an osmoreceptor mechanism in the hepatoportal system was first suggested by Haberich and his colleagues on the basis of the fact that very small amounts of water or hypertonic saline infused into the portal vein produce diuresis or antidiuresis in the rats and that these effects can be abolished by cutting the hepatic branch of the vagus [8,11]. However, Schneider et al. [20] carried out an experiment similar to that of Haberich in conscious dogs and failed to provide evidence for an osmoreceptor mechanism in the liver. The contradictory results of Haberich and Schneider et al. suggest a species difference in hepatic osmoreception. It is likely that there is a species difference particularly in regulatory mechanism of water balance between animals which live by a river and in a desert, possibly between a herbivore, a carnivore and an omnivore. In case of disagreements, discussions should be confined to consideration of the same species. No electrophysiological evidence had been reported until that resulting from the preliminary work on the guinea-pigs by Niijima [16]. He presented neurophysiological evidence suggesting that there are osmoreceptors in the liver of the guinea pig. This hepatic osmoreceptor was affected by mannose, glucose and sucrose as well as by NaC1. These results are at variance with those reported by Andrews and Orbach
272
© ISO
© O
IO0
ItO
m20
130
140
•
•
I$O
,to
~o~
O
50
Fig. 2. Solid circles show that responses of one type of fiber are positivelycorrelated with increases in osmotarity; open circles show that responses of another type of fiber are correlated with decreases in osmolarity. Ordinate: percent of base-line discharge rate. Abscissa: concentrations of NaCI in mM contained in test solutions. [5] who suggested that only a sodium receptor, not a true osmoreceptor, was involved in production of discharge in the hepatic vagus of the rabbit. Thus, Adachi et al. [1] confirmed that osmoreceptive afferent fibers exist in the hepatic branch of the vagus in the rat. In these studies also behavioral techniques were used to ascertain the physiological meaning of such an afferent system on the regulation of water balance. The rat liver was perfused with Ringer solution through the portal vein by use of a perfusion system which was designed to switch from standard Ringer solution to hypertonic or hypotonic Ringer solution. Neural responses to the osmotic changes m the perfusion solutions were analyzed. They showed that two dlffrent types of osmosensitive afferent fibers exist in the hepatic vagus; one increases the diseha~e rate in response to higher osmotic pressure, while the other shows a similar response to lower osmotic pressure (Fig. 2). Behavioral chanses caused by hepatic vagotomy were observed. Though no d i f f e i ~ c e s could be detected in routine behavior (e.g. daily intakes of food and water, body weight increase) between the vagotomized and the sham-operated rats, the former lost the ability to adjust urine concentration immediately in response to osmotic changes in the internal environment. It is concluded that a hepatic osmoreceptor mechanism exists in the rats and transmits the signals to the central nervous system via the vagus. However, there is no reason for concluding that this mechar.lsm plays a predominant role in isoosmotic regulation or dominates all other systems which detect osmotic change.
Ad,mwlHIllamS The author wishes to thank Miss K ~ ~ a t a for t~ing: Lhe ma.-lu~ript. This work was s u ~ e d by a research grant f r ~ ~ Japanese ~ $ ~ of ~tion,
273
References 1 Adachi, A., Niijima, A. and Jacobs, H.L., An hepatic osmoreceptor mechanism in the rat: electrophysiological and behavioral studies, Amer. J. Physiol., 231 (1976) 1043-1049. 2 Adachi, A. and Niijima, A., Thermosensitive afferent fibers in the hepatic branch of the vagus nerve in the guinea pig, J. auton. Nerv. System., 5 (1982) 101-109. 3 Adair, E.R., Evaluation of some controller inputs to behavioral temperature regulation, Int. J. Biometeoroi., 15 (1971) 121-128. 4 Anand, B.K., Nervous regulation of food intake, Physiol. Rev., 41 (1961) 677-708. 5 Andrews, W.H.H. and Orbach, J., Sodium receptors activating some nerves of perfused rabbit livers, Amer. J. Physiol., 227 (1974) 1273-1275. 6 Boman, K.K.A. and Hensel, H., Afferent impulses in cutaneous sensory nerves in conscious human subjects, J. Neurophysiol., 193 (1960) 564-578. 7 Brobeck, J.R., Food intake as mechanism of temperature regulation, Yale J. Biol. Med., 20 (1948) 545-552. 8 Dennhardt, R., Ohm, W.W. and Haberich, F.J., Die Ausschaltung der Leber~te des N. vagus an der wachen Ratte und ihr Einfluss auf die hepatogene Diurese-indirekter Beweis fi~r die afferente Leitung der Leber-Osmoreceptoren i~ber den N. vagus, Pfli~ger's Arch. ges. Physiol., 328 (1971) 51-56. 9 DiBella, L. and Tarozzi, G., Probable liver thermoreceptors as modulators of food and water intake (Abstr.), Int. Congr. Physiol. Sci. 26th Jerusalem Satellite Symp., 1974. 10 Downey, J.A., Mattram, R.F. and Picketing, G.W., The location by regional cooling of central temperature receptors in the conscious rabbit, J. Physiol. (Lond.), 170 (1964) 415-441. 11 Habetich, F.J., Osmoreception in the portal circulation, Fed. Proc., 27 (1968) 1137-1141. 12 Hensel, H., Iggo, A. and Witt, I., A quantitative study of sensitive cutaneous thermoreceptors with C afferent fibers, J. Physiol. (Lond.), 153 (1960) 113-126. 13 lggo, A., Cutaneous thermoreceptors in primates and sub-primates, J. Physiol. (Lond.), 200 (1969) 403-430. 14 Kennedy, G.C., Role of depot fat in hypothalamic control of food intake in rat, Proc. roy. Soc. B, 140 (1953) 578-592. 15 Nakayama, T., Hammei, H.T., Hardy, J.D. and Eisenman, J.S., Thermal stimulation of electrical activity of single units of preoptic region, Amer. J. Physiol., 204 (1963) 1122-1126. 16 Niijima, A., Afferent discharges from osmoreceptors in the liver of the guinea pig, Science, 166 (1969) 1519-1520. 17 Rawson, R.D., Thermoregulatory responses to intra-abdominal heating in sheep, Physiologist, 12 (1969) 337. 18 Riedel, W., Siaplauras, G. and Simon, E., Intra-abdominal thermosensitivity in the rabbit as compared with spinal thermosensitivity, Pfliiger's Arch. ges., Physiol., 340 (1973) 59-70. 19 Sawchenko, P.E. and Friedman, M.I., Sensory functions of the liver-a review, Amer. J. Physiol., 236 (1979) R5-R20. 20 Schneider, E.G., Davis, J.O., Robb, C.A., Baumber, J.S., Johnson, J.A. and Wright, F.S., Lack of evidence for a hepatic osmoreceptor mechanism in conscious dogs, Amer. J. Physiol., 218 (1970) 42-45. 21 Simon, E., Rautenberg, W., Thauer, R. and Itiki, M., AusliSsung thermoregulatorischer Reaktion dutch lokale Kiahlung im Vertebralkanal, Naturwissenschaften, 50 (1963) 337. 22 Strominger, J.L. and Brobeck, J.R., Mechanism of regulation of food intake, Yale J. Biol. Med., 25 (1953) 383-390. 23 Trazzi, G., DiBeila, L., Scalera, G. and Rossi, M.T., Role of proprioceptive masticatory feedback in the rat feeding pattern behavior, Nutr. Metab., 21 Suppl. 1 (1977) 70-72. 24 Thompson, F.J. and Barnes, C.D., Evidence for thermosensitive elements in the femoral vein, Life Sci., 91 (1970) 309-312. 25 Zotterman, Y., Specific actionpotentials in lingual nerve of cat, Scand. Arch. Physiol., 75 (1936) 105-120.