- Email: [email protected]
Histamine synthesis and degradation in the chick (Gallus gallus) and the rat (Rattus rattus)
Comp. Biochera. PhysioL, Vol. 64C, pp. 227 to 228
0306-4492/79/1001-0227502.00/0
© Pergamon Press Ltd 1979, Printed in Greal Britain
HISTAMINE SYNTHESIS AND D E G R A D A T I O N IN THE C H I C K (GALLUS GALLUS) AND THE RAT
(RATTUS RATTUS)* TERU ISHIBASHI,OLGA DONIS, DENNIS FITZPATRICK,N ~ Soo LEE and HANS FISHERt Department of Nutrition, Rutgers University, New Brunswick, New Jersey 08903, U.S.A. (Received 23 April 1979) Abstraet--l. Seven tissue~ from chicks (180g body weight) and rats (100g body weight) were examined for histamine and the enzymes histidine decarboxylase and histamine methyl transferase. 2. The greatest histamine concentration was found in the stomach of both species. 3. The tissue concentrations of histamine in the rat and chick could not be explained on the basis of the activity of the synthesizing and degradatory enzymes. 4. Major species differences in enzyme activity were observed, with the chick values corresponding more nearly with reported literature values for the mouse and the guinea-pig than for the rat.
INTRODUCTION Maslinski (1975) has recently published a comprehensive review of histamine biogenesis, metabolism and physiological activity. The physiological roles of histamine are well-documented and include effects on microcirculation, vascular permeability, smooth muscle contraction, gastric secretion, and finally, histamine is also reputed to be a brain neurotransmitter. A high histamine-forming capacity is associated with fast growing tissues, such as fetal or wound tissue. Kahlson et al. (1960) noted that in spite of the enhanced histamine forming capacity of wound tissue, the histamine content of these tissues was much lower than that of intact skin. They suggested that "nascent" histamine had a specialized action that could not be fulfilled by extracellular histamine. While the metabolic pathways for histamine synthesis and degradation are known, the regulatory controls for tissue histamine levels remain elusive. Huszti et al. (1977) on the basis of measuring only histidine decarboxylase activity of rat stomach suggested that "the effhix rather than the formation of histamine might be regulatory for the actual concentrations of histamine". We are not aware of any study in which histamine and its synthesizing and degradatory enzymes have been examined simultaneously in the same tissues. While the rat has often been the laboratory animal of choice in histamine-related studies, Brown "et al. (1959) reported considerable differences in HMTase activity between rat tissues and tissues of mouse and guinea-pig. In this study, seven different tissues from chicks and rats were examined to explore their relative importance in histamine metabolism. Tissue concentrations of histidine and histamine as well as the activities of the synthesizing enzyme histidine decarb* Paper of the Journal Series, New Jersey Agricultural Experiment Station. Supported in part by U.S. Public Health Service Grant 1R01 AM 18932 and by the Charles and Johann.a Busch Memorial Fund. t To whom reprint requests should be addressed.
oxylase (HDase, EC 4.1.1.2.2) and the degradatory enzyme, histamine methyl transferase (HMTase, EC 2.1.1.8.) were measured and compared. The results indicated interesting species and tissue differences in relation to histamine concentrations and the synthesizing and degradatory enzyme activities. MATERIALS AND METHODS Weaned, male Wistar rats (Rattus rattus) received a commercial rat chow providing 22.3% protein with 0.58% histidine until a body weight of 100g was attained. White Leghorn male chicks (Gallus ffaUus) were fed a purified diet supplying 12% protein with 0.8% histidine until a body weight of 180g was attained. Four rats and four chicks were killed by decapitation, and their tissues excised and weighed. Histidine,' histamine and HMTase activity were assayed by a modification of the m~thod of Taylor & Snyder (1972). HDase activity was determined by a modification of the method of Snyder & Epps (1968).
RESULTS The. concentrations of histidine and histamine as well as the activities of HDase and HMTase differed among the tissues and species examined (Table 1). Histidine concentrations were greater by 50% in chick brain compared to rat brain. Chick kidney concentrations were also somewhat greater than rat kidney levels. Histamine concentrations were generally similar in the chick and the rat with two exceptions: rat muscle and chick kidney had a greater histamine content than did chick muscle and rat kidney. The greatest histamine concentration was found in the stomach (or proventriculus) of both species. In the rat stomach, the high histamine concentration was associated with a low HMTase enzyme activity and a high HDase activity. In the chick proventriculus, the high histamine concentration was associated with a low activity of the synthesizing HDase enzyme while the activity of HMTase, the degradatory enzyme, was highest in this organ.
227
TERU ISHIBASHIet aL
228
Table 1. Tissue histamine and histidine concentrations, and activities of the enzymes histidine decarboxylase and histamine methyitransferase in rats and chicks Histidine (nmol/g) Tissue
Rat
Whole brain Musclei" Stomach:~ Liver Ileum Pancreas Kidney§
Chick
190_ 14" 277+7 268+11 303 + 3 6 280 + 24 184-t-45 245_+11
HDase (nmol/g/br)
Histamine (nmol/g) Rat
303 + 12 9.2 Jr 0.4 305+ 12 73.9__+3.4 231-t-9 122.4::1:11.7 317_9 9.5__+0.3 246 + 9 32.5 + 0.5 207_+8 18.9___0.3 287___8 10.0 _ 0.1
HMTase (#mol/g/hr)
Chick
Rat
Chick
Rat
Chick
9.4+ 1.0 16.6+0.8 101.2-t-4.1 21.9+ 1.6 26.0 + 3.5 51.7+2.6 16.0_+1.5
227+ 14 117+ 10 3860+880 427+51 324 ___24 123-t-40 3054-29
610__+ 18 780:t:20 255-1-11 251 + 2 9 365 + 44 389±11 1356+181
17.9 + 1.0 1.0+0.4 2.1+0.1 8.4+0.1 20.8 + 0.9 2.4_+0.2 83.1___4.4
3.2+0.1 4.3 + 0.2 101.5 + 12.0 95.3 ___8.4 21.2 ___ 1.4 17.5 ___0.5 41.9 ___ 1.2
* Mean value with its standard error for 4 analyses each from rats and chicks. l" In rats, muscle sample was from tibialis anterior and extensor digitorum long., in chicks, sample was from pectoralis major. :I:In chicks, proventriculus. § Left kidney in both species.
The highest HDase activity in the chick occurred in the kidney, followed by muscle and brain tissue. In the rat, all tissues except stomach, which was exceptionally high, had lower HDase activities than did chick kidney, muscle or brain. The highest HMTase activity in the rat was observed in kidney, while for the chick the proventriculus and liver had the highest activities. DISCUSSION In comparing the enzyme activities in the tissues examined, it is striking to note, that the degradatory enzyme, HMTase, is present in far greater concentrations than the synthesizing enzyme, HDase. T h e only exception is the greater HDase activity in rat stomach, which may account for the high histamine concentration in this tissue. Reilly & Schayer (1968) believe that stomach histamine synthesis is an important regulator for histamine concentrations in other tissues. While this may explain our findings for the rat, it provides no insight into the interrelationship between histamine and its metabolic enzymes in the chick. The chick stomach (proventriculus) histamine concentration was the greatest among the chick tissues examined, in agreement with rat stomach. However, unlike rat stomach, the HDase activity was the lowest and the HMTase activity the highest for the chick tissues analyzed. It seems clear that the regulation of tissue histamine levels is more complex than a balancing between synthesizing and degradatory enzymes, as suggested by Huszti eral. (1977). Brown et al. (1959) reported the distribution of H M T a s e enzyme activity of various tissues in a number of species in relation to that of guinea-pig brain. The HMTase activity ratios of rat tissues in this study agree well with the values reported by Brown for the rat. The H M T a s e activity ratios observed in this study for chick tissues were similar to the values reported by Brown for the guinea-pig and the mouse. In view of the considerable differences
in HMTase activity between the rat on one hand, and the guinea-pig, mouse and chick, on the other, caution must be exercised in extrapolating results from rats to other animal species. SUMMARY The highest tissue histamine concentration in both chick and rat was found in the stomach. In the rat, this tissue had the highest HDase and among the lowest HMTase activity. In the chick, the highest HDase activity was found in the kidney, while stomach and liver had the highest HMTase activity. Tissue concentrations of histamine could not be explained on the basis of synthesizing and degradatory enzyme concentrations. REFERENCES BROWN D. D., TOMCHICK R: & AXELROD J. (1959) The distribution and properties of a histamine-methylating enzyme. J. biol. Chem. 234, 2948-2950. HUSZTI Z., KENNESSEYA., KURT1 M. & SOURKES T. L. (1977) Nonmast cell histamine levels in rat tissues after histidine loading. Eur. J. Pharmac. 42, 231-240. K~LSON G., NILSSO~ K., ROSENGRENE. & Z~DER~LDT B. (1960) Wound healing as dependent on rate of histamine formation. Lancet ii, 230-234. M~LINSm C. (1975) Histamine and its metabolism in mammals. Part I: Chemistry and formation of histamine. Part II: Catabolism of histamine and histamine liberation. Agents & Actions 5, 89-106 and 182-225. REILLY M. A. & SCHAYERR. W. (19688) Further studies on the histidinc-histamine relationship in vivo: effects of endotoxin and of histidine dccarboxylasc inhibitors. Br. J. Pharmac. 34, 551-563. SNYDER S. H. & EPPS L. (1968) Regulation of histidine dccarboxylase in rat stomach by gastrin: the effect of inhibitors of protein synthesis. Mol. Pharmac. 4, 187-195. TAYLORK. M. & SNYD~ S. H. (1972) Isotopic microassay of histamine, histidine, histidine dccarboxylas¢ and histamine methyltransferasc in brain tissue. J. Neurochem. 19, 1343-1358.
0306-4492/79/1001-0227502.00/0
© Pergamon Press Ltd 1979, Printed in Greal Britain
HISTAMINE SYNTHESIS AND D E G R A D A T I O N IN THE C H I C K (GALLUS GALLUS) AND THE RAT
(RATTUS RATTUS)* TERU ISHIBASHI,OLGA DONIS, DENNIS FITZPATRICK,N ~ Soo LEE and HANS FISHERt Department of Nutrition, Rutgers University, New Brunswick, New Jersey 08903, U.S.A. (Received 23 April 1979) Abstraet--l. Seven tissue~ from chicks (180g body weight) and rats (100g body weight) were examined for histamine and the enzymes histidine decarboxylase and histamine methyl transferase. 2. The greatest histamine concentration was found in the stomach of both species. 3. The tissue concentrations of histamine in the rat and chick could not be explained on the basis of the activity of the synthesizing and degradatory enzymes. 4. Major species differences in enzyme activity were observed, with the chick values corresponding more nearly with reported literature values for the mouse and the guinea-pig than for the rat.
INTRODUCTION Maslinski (1975) has recently published a comprehensive review of histamine biogenesis, metabolism and physiological activity. The physiological roles of histamine are well-documented and include effects on microcirculation, vascular permeability, smooth muscle contraction, gastric secretion, and finally, histamine is also reputed to be a brain neurotransmitter. A high histamine-forming capacity is associated with fast growing tissues, such as fetal or wound tissue. Kahlson et al. (1960) noted that in spite of the enhanced histamine forming capacity of wound tissue, the histamine content of these tissues was much lower than that of intact skin. They suggested that "nascent" histamine had a specialized action that could not be fulfilled by extracellular histamine. While the metabolic pathways for histamine synthesis and degradation are known, the regulatory controls for tissue histamine levels remain elusive. Huszti et al. (1977) on the basis of measuring only histidine decarboxylase activity of rat stomach suggested that "the effhix rather than the formation of histamine might be regulatory for the actual concentrations of histamine". We are not aware of any study in which histamine and its synthesizing and degradatory enzymes have been examined simultaneously in the same tissues. While the rat has often been the laboratory animal of choice in histamine-related studies, Brown "et al. (1959) reported considerable differences in HMTase activity between rat tissues and tissues of mouse and guinea-pig. In this study, seven different tissues from chicks and rats were examined to explore their relative importance in histamine metabolism. Tissue concentrations of histidine and histamine as well as the activities of the synthesizing enzyme histidine decarb* Paper of the Journal Series, New Jersey Agricultural Experiment Station. Supported in part by U.S. Public Health Service Grant 1R01 AM 18932 and by the Charles and Johann.a Busch Memorial Fund. t To whom reprint requests should be addressed.
oxylase (HDase, EC 4.1.1.2.2) and the degradatory enzyme, histamine methyl transferase (HMTase, EC 2.1.1.8.) were measured and compared. The results indicated interesting species and tissue differences in relation to histamine concentrations and the synthesizing and degradatory enzyme activities. MATERIALS AND METHODS Weaned, male Wistar rats (Rattus rattus) received a commercial rat chow providing 22.3% protein with 0.58% histidine until a body weight of 100g was attained. White Leghorn male chicks (Gallus ffaUus) were fed a purified diet supplying 12% protein with 0.8% histidine until a body weight of 180g was attained. Four rats and four chicks were killed by decapitation, and their tissues excised and weighed. Histidine,' histamine and HMTase activity were assayed by a modification of the m~thod of Taylor & Snyder (1972). HDase activity was determined by a modification of the method of Snyder & Epps (1968).
RESULTS The. concentrations of histidine and histamine as well as the activities of HDase and HMTase differed among the tissues and species examined (Table 1). Histidine concentrations were greater by 50% in chick brain compared to rat brain. Chick kidney concentrations were also somewhat greater than rat kidney levels. Histamine concentrations were generally similar in the chick and the rat with two exceptions: rat muscle and chick kidney had a greater histamine content than did chick muscle and rat kidney. The greatest histamine concentration was found in the stomach (or proventriculus) of both species. In the rat stomach, the high histamine concentration was associated with a low HMTase enzyme activity and a high HDase activity. In the chick proventriculus, the high histamine concentration was associated with a low activity of the synthesizing HDase enzyme while the activity of HMTase, the degradatory enzyme, was highest in this organ.
227
TERU ISHIBASHIet aL
228
Table 1. Tissue histamine and histidine concentrations, and activities of the enzymes histidine decarboxylase and histamine methyitransferase in rats and chicks Histidine (nmol/g) Tissue
Rat
Whole brain Musclei" Stomach:~ Liver Ileum Pancreas Kidney§
Chick
190_ 14" 277+7 268+11 303 + 3 6 280 + 24 184-t-45 245_+11
HDase (nmol/g/br)
Histamine (nmol/g) Rat
303 + 12 9.2 Jr 0.4 305+ 12 73.9__+3.4 231-t-9 122.4::1:11.7 317_9 9.5__+0.3 246 + 9 32.5 + 0.5 207_+8 18.9___0.3 287___8 10.0 _ 0.1
HMTase (#mol/g/hr)
Chick
Rat
Chick
Rat
Chick
9.4+ 1.0 16.6+0.8 101.2-t-4.1 21.9+ 1.6 26.0 + 3.5 51.7+2.6 16.0_+1.5
227+ 14 117+ 10 3860+880 427+51 324 ___24 123-t-40 3054-29
610__+ 18 780:t:20 255-1-11 251 + 2 9 365 + 44 389±11 1356+181
17.9 + 1.0 1.0+0.4 2.1+0.1 8.4+0.1 20.8 + 0.9 2.4_+0.2 83.1___4.4
3.2+0.1 4.3 + 0.2 101.5 + 12.0 95.3 ___8.4 21.2 ___ 1.4 17.5 ___0.5 41.9 ___ 1.2
* Mean value with its standard error for 4 analyses each from rats and chicks. l" In rats, muscle sample was from tibialis anterior and extensor digitorum long., in chicks, sample was from pectoralis major. :I:In chicks, proventriculus. § Left kidney in both species.
The highest HDase activity in the chick occurred in the kidney, followed by muscle and brain tissue. In the rat, all tissues except stomach, which was exceptionally high, had lower HDase activities than did chick kidney, muscle or brain. The highest HMTase activity in the rat was observed in kidney, while for the chick the proventriculus and liver had the highest activities. DISCUSSION In comparing the enzyme activities in the tissues examined, it is striking to note, that the degradatory enzyme, HMTase, is present in far greater concentrations than the synthesizing enzyme, HDase. T h e only exception is the greater HDase activity in rat stomach, which may account for the high histamine concentration in this tissue. Reilly & Schayer (1968) believe that stomach histamine synthesis is an important regulator for histamine concentrations in other tissues. While this may explain our findings for the rat, it provides no insight into the interrelationship between histamine and its metabolic enzymes in the chick. The chick stomach (proventriculus) histamine concentration was the greatest among the chick tissues examined, in agreement with rat stomach. However, unlike rat stomach, the HDase activity was the lowest and the HMTase activity the highest for the chick tissues analyzed. It seems clear that the regulation of tissue histamine levels is more complex than a balancing between synthesizing and degradatory enzymes, as suggested by Huszti eral. (1977). Brown et al. (1959) reported the distribution of H M T a s e enzyme activity of various tissues in a number of species in relation to that of guinea-pig brain. The HMTase activity ratios of rat tissues in this study agree well with the values reported by Brown for the rat. The H M T a s e activity ratios observed in this study for chick tissues were similar to the values reported by Brown for the guinea-pig and the mouse. In view of the considerable differences
in HMTase activity between the rat on one hand, and the guinea-pig, mouse and chick, on the other, caution must be exercised in extrapolating results from rats to other animal species. SUMMARY The highest tissue histamine concentration in both chick and rat was found in the stomach. In the rat, this tissue had the highest HDase and among the lowest HMTase activity. In the chick, the highest HDase activity was found in the kidney, while stomach and liver had the highest HMTase activity. Tissue concentrations of histamine could not be explained on the basis of synthesizing and degradatory enzyme concentrations. REFERENCES BROWN D. D., TOMCHICK R: & AXELROD J. (1959) The distribution and properties of a histamine-methylating enzyme. J. biol. Chem. 234, 2948-2950. HUSZTI Z., KENNESSEYA., KURT1 M. & SOURKES T. L. (1977) Nonmast cell histamine levels in rat tissues after histidine loading. Eur. J. Pharmac. 42, 231-240. K~LSON G., NILSSO~ K., ROSENGRENE. & Z~DER~LDT B. (1960) Wound healing as dependent on rate of histamine formation. Lancet ii, 230-234. M~LINSm C. (1975) Histamine and its metabolism in mammals. Part I: Chemistry and formation of histamine. Part II: Catabolism of histamine and histamine liberation. Agents & Actions 5, 89-106 and 182-225. REILLY M. A. & SCHAYERR. W. (19688) Further studies on the histidinc-histamine relationship in vivo: effects of endotoxin and of histidine dccarboxylasc inhibitors. Br. J. Pharmac. 34, 551-563. SNYDER S. H. & EPPS L. (1968) Regulation of histidine dccarboxylase in rat stomach by gastrin: the effect of inhibitors of protein synthesis. Mol. Pharmac. 4, 187-195. TAYLORK. M. & SNYD~ S. H. (1972) Isotopic microassay of histamine, histidine, histidine dccarboxylas¢ and histamine methyltransferasc in brain tissue. J. Neurochem. 19, 1343-1358.