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Effect of aging on response of guinea pig trachea to isoprenaline
2405 Ginsberg, F., 1982, J. Int. Med. Res., 10, 209-213. Mangan, F.R. et al., 1981, 15th Int. Cong. Rheum., Paris, Abs. 1451. P.fr.342 [
Effects of d-nicotine on contraction and relaxation induced by l-nicotine in the tracheal and main bronchial preparations of guinea pig and rabbit F u n a y a m a *, N., Moriya, M. and Takayanagi~ !. Dept. of Chemical Pharmacology, Toho University School of Pharmaceutical Science. Funabashi Chiba 274 and * Dept. of Research and Development, Horiuchi Itaro and Co., Ltd.. Chiyoda-kug Tokyo 101. Japan
Pharmacological action of 1- and d-isomers of nicotine were studied in the airway smooth muscle preparations of guinea pig and rabbit. Experimental animals, which were male guinea pig (Hartley strain) weighing between 250 g-350 g and male rabbit (New Zealand White strain) weighing between 2.5 kg-3.5 kg, were stunned by a blow on the back of the neck, exsanguinated and removed trachea and main bronchus. Main bronchial preparations of guinea pig and rabbit were dissected from lung tissue and cut helically (Takayanagi and Kizawa,1985). Tracheal preparation of guinea pig was cut helically, but the trachea of rabbit was cut transversly between the segment of cartilage, so as to give a number of ring of tracheal muscle. Some of them were tied together with cotton and used as a tracheal chain preparation. These preparations were suspended in a 10 ml organ bath filled Krebs solution, kept at 37 ° C and gassed with carbogen. Responses of the preparations to drugs were recorded isotonicaly under a tenssion of 0.5 g. l-Nicotine produced biphasic response in the guinea pig trachea, which consists of an initial contraction followed by a large rel~ation but in the guinea pig main bronchus only contraction was produced by l-nicotine (Takayanagi al., 1984a). However, l-nicotine produced only contraction in both trachea and main bronchus of rabbit (Takayana .... et al., 1984b). d-Nicotine (~_ 3 × 10 -4 M) produced relaxation in the guinea pig trachea in a concentration depende. manner, while d-nicotine did not produce any effect on the other airway preparations, d-Nicotine declined concew.ration contractile- or relaxation-response curves of l-nicotine in all the airway preparations. Contractile responses of guinea pig and rabbit tracheas to l-nicotine were completely blocked by d-nicotine (10-4M) while d-nicotine (10 -4 M) considerably inhibited contractions of guinea pig and rabbit bronchi, and relaxation of guinea pig trachea induced by l-nicotine. Similar results were obtained in the presence low concentrations of l-nicotine instead of d-nicotine. Nicotinic agonists are known te cause inhibitory effects on the subsequently administered nicotinic stimuli. Therefore, the inhibition of response to l-nicotine by d-nicotine is considered to be due to nicotinic desensitization. References Takayanagi, I. and Y. Kizawa, 1985, Eur. J. Pharmacol. 113, 319. Takayanagi, I., Y. Kizawa and H. Sone, 1984a, Gen. Pharmac. 15, 349. Takayanagi, I., Y.Kizawa and T. Hiruta, 1984b, Eur.J. Pharmacol. 104, 351. P.fr.343 [
Effect of aging on response of guinea pig trachea to isoprenaline Takayanagi, I., Kawano, K.-I. and Koike, K. Department of Chemical Pharmacology. Toho University of Pharmaceutical Sciences. Funabashi. Chiba 274. Japan
To study the effect of aging on beta-adrenergic potency of iso-prenaline, tracheas from 3, 6, 10, 40 and 100 week old guinea pigs were used as test tissues. The tracheal preparation was suspended in a physiological solution kept at 32°C and gassed with carbogen. The physiological solution contained ascorbic acid (10 -3 M), desmethylimipramine (10 -~ M) and pargyline (10 -6 M) to inhibit the oxidation and neural uptake of catecholamine and monoamine
2406 oxidase. To block alpha-adrenoceptors the solution also contained phentolamine (10 -6 M). The pD2 values (potency) of isoprenaline increased with age in tracheas treated with corticosterone (3 × 10-5 M) but decreased in untreated tracheas. The pA2 value of propranolol against isoprenaline estimated in the treated tracheas did not change with age. Specific binding of 3H-dihydroalprenolol to the microsomal fractions from the tracheal muscles from 6, 10 and 40 week old guinea pigs N-as analyzed with Scatchard plot. The capacity of maximum binding sites of 3H-dihydroalprenolol increased with increasing age, while its dissociation constant did not change. Age-related increase in potency of isoprenaline in the tracheas treated with corticosterone is considered to be due to the increase in total amount (density) of beta-adrenoceptors, as reported in post alphal-adrenoceptors in rat aorta and vas deferens (Takayanagi et al., 1987, 1989). Howe~r, potency of the chug in untreated tracheas decreased with age. These results suggest that extrancuronal uptake plays an important role in beta-adrenergic action of isoprenaline in older (40 and 100 weeks) guinea pigs.
Reg~ Takayanagi, I., Maeda, (3. and Koike, IC, 1987, J. Pharm. Pharmacol. 39, 754. Taka.vanagi, L, Shinkai, M. and Yamasawa, K., 1989, Can. J. Physiol. Pharmacol. 67 (12) in press.
I
1 Effects of capsaicin on isolated guinea-pig smooth muscles Cingi, M.I., Erol, K, C)zdemir, M. a n d Cingi, C. Dept. of Pharmacology, Medical School, Anadolu University, Eski~ehir, Turkey
Recent findings indicate that capsaicin (CAP) produces a neurogenic relaxation of the rat duodenum by activating an intramural non-adrenergic mechanism which inhibits intestinal motility (Maggi, 1988). Experimental evidence indicates that, in rats, a CAP sensitive mechanism regulates the micturition threshold by relaying to the central nervous system information on the volume of fluid present in the bladder (Sharkey, 1983). In particular, topical application of CAP on the bladder dome activates a series of neurogenic rhythmic contractions which were assumed to correspond to the micturition reflex (Maggi, 1988), while systemic CAP desensitization increases bladder capacity (Santicioli, 1985). Recent evidence indicates that multiple neuropeptides are co-released by CAP both centrally and peripherally (Maggi, 1988), To date, at least 12 different types of peptide-like immunoreactivities were reported to be present in CAP-sensitive nerves. The present communication deals with the effect of capsaick~ on the motility of the isolated guinea-pig urinary bladder, ileum, colon and gall bladder. After decapitation of the animals, their smooth muscles were quickly removed and placed in a 10-ml organ bath (37°C) in Krebs solution (bubbled 95% 02, 5~; CO2) under a resting tension of 1 g. CAP (10 -5 M) produced a contraction in the urinary bladder. A second administration of CAP reduced the amplitude of contractions, indicating desensitization. CAP produced a concentration-dependent contraction on the ileal segments. Biphasic effects were observed on the colon; CAP caused a contraction in low doses (10 -7 M), but a relaxation in high dose (10 -5 M). Contractions occurred in the gall bladder but desensitization was not observed.
References Maggi, C.A. et al. Gen. Pharmac. 1988, 19 (1) 1-43. Santiciofi, P. et al. J. Urol. 1985, 133, 700-704. Sharkey, K.A. et aLl.Neuroscience 1983, 10, 861-86°.
Effects of d-nicotine on contraction and relaxation induced by l-nicotine in the tracheal and main bronchial preparations of guinea pig and rabbit F u n a y a m a *, N., Moriya, M. and Takayanagi~ !. Dept. of Chemical Pharmacology, Toho University School of Pharmaceutical Science. Funabashi Chiba 274 and * Dept. of Research and Development, Horiuchi Itaro and Co., Ltd.. Chiyoda-kug Tokyo 101. Japan
Pharmacological action of 1- and d-isomers of nicotine were studied in the airway smooth muscle preparations of guinea pig and rabbit. Experimental animals, which were male guinea pig (Hartley strain) weighing between 250 g-350 g and male rabbit (New Zealand White strain) weighing between 2.5 kg-3.5 kg, were stunned by a blow on the back of the neck, exsanguinated and removed trachea and main bronchus. Main bronchial preparations of guinea pig and rabbit were dissected from lung tissue and cut helically (Takayanagi and Kizawa,1985). Tracheal preparation of guinea pig was cut helically, but the trachea of rabbit was cut transversly between the segment of cartilage, so as to give a number of ring of tracheal muscle. Some of them were tied together with cotton and used as a tracheal chain preparation. These preparations were suspended in a 10 ml organ bath filled Krebs solution, kept at 37 ° C and gassed with carbogen. Responses of the preparations to drugs were recorded isotonicaly under a tenssion of 0.5 g. l-Nicotine produced biphasic response in the guinea pig trachea, which consists of an initial contraction followed by a large rel~ation but in the guinea pig main bronchus only contraction was produced by l-nicotine (Takayanagi al., 1984a). However, l-nicotine produced only contraction in both trachea and main bronchus of rabbit (Takayana .... et al., 1984b). d-Nicotine (~_ 3 × 10 -4 M) produced relaxation in the guinea pig trachea in a concentration depende. manner, while d-nicotine did not produce any effect on the other airway preparations, d-Nicotine declined concew.ration contractile- or relaxation-response curves of l-nicotine in all the airway preparations. Contractile responses of guinea pig and rabbit tracheas to l-nicotine were completely blocked by d-nicotine (10-4M) while d-nicotine (10 -4 M) considerably inhibited contractions of guinea pig and rabbit bronchi, and relaxation of guinea pig trachea induced by l-nicotine. Similar results were obtained in the presence low concentrations of l-nicotine instead of d-nicotine. Nicotinic agonists are known te cause inhibitory effects on the subsequently administered nicotinic stimuli. Therefore, the inhibition of response to l-nicotine by d-nicotine is considered to be due to nicotinic desensitization. References Takayanagi, I. and Y. Kizawa, 1985, Eur. J. Pharmacol. 113, 319. Takayanagi, I., Y. Kizawa and H. Sone, 1984a, Gen. Pharmac. 15, 349. Takayanagi, I., Y.Kizawa and T. Hiruta, 1984b, Eur.J. Pharmacol. 104, 351. P.fr.343 [
Effect of aging on response of guinea pig trachea to isoprenaline Takayanagi, I., Kawano, K.-I. and Koike, K. Department of Chemical Pharmacology. Toho University of Pharmaceutical Sciences. Funabashi. Chiba 274. Japan
To study the effect of aging on beta-adrenergic potency of iso-prenaline, tracheas from 3, 6, 10, 40 and 100 week old guinea pigs were used as test tissues. The tracheal preparation was suspended in a physiological solution kept at 32°C and gassed with carbogen. The physiological solution contained ascorbic acid (10 -3 M), desmethylimipramine (10 -~ M) and pargyline (10 -6 M) to inhibit the oxidation and neural uptake of catecholamine and monoamine
2406 oxidase. To block alpha-adrenoceptors the solution also contained phentolamine (10 -6 M). The pD2 values (potency) of isoprenaline increased with age in tracheas treated with corticosterone (3 × 10-5 M) but decreased in untreated tracheas. The pA2 value of propranolol against isoprenaline estimated in the treated tracheas did not change with age. Specific binding of 3H-dihydroalprenolol to the microsomal fractions from the tracheal muscles from 6, 10 and 40 week old guinea pigs N-as analyzed with Scatchard plot. The capacity of maximum binding sites of 3H-dihydroalprenolol increased with increasing age, while its dissociation constant did not change. Age-related increase in potency of isoprenaline in the tracheas treated with corticosterone is considered to be due to the increase in total amount (density) of beta-adrenoceptors, as reported in post alphal-adrenoceptors in rat aorta and vas deferens (Takayanagi et al., 1987, 1989). Howe~r, potency of the chug in untreated tracheas decreased with age. These results suggest that extrancuronal uptake plays an important role in beta-adrenergic action of isoprenaline in older (40 and 100 weeks) guinea pigs.
Reg~ Takayanagi, I., Maeda, (3. and Koike, IC, 1987, J. Pharm. Pharmacol. 39, 754. Taka.vanagi, L, Shinkai, M. and Yamasawa, K., 1989, Can. J. Physiol. Pharmacol. 67 (12) in press.
I
1 Effects of capsaicin on isolated guinea-pig smooth muscles Cingi, M.I., Erol, K, C)zdemir, M. a n d Cingi, C. Dept. of Pharmacology, Medical School, Anadolu University, Eski~ehir, Turkey
Recent findings indicate that capsaicin (CAP) produces a neurogenic relaxation of the rat duodenum by activating an intramural non-adrenergic mechanism which inhibits intestinal motility (Maggi, 1988). Experimental evidence indicates that, in rats, a CAP sensitive mechanism regulates the micturition threshold by relaying to the central nervous system information on the volume of fluid present in the bladder (Sharkey, 1983). In particular, topical application of CAP on the bladder dome activates a series of neurogenic rhythmic contractions which were assumed to correspond to the micturition reflex (Maggi, 1988), while systemic CAP desensitization increases bladder capacity (Santicioli, 1985). Recent evidence indicates that multiple neuropeptides are co-released by CAP both centrally and peripherally (Maggi, 1988), To date, at least 12 different types of peptide-like immunoreactivities were reported to be present in CAP-sensitive nerves. The present communication deals with the effect of capsaick~ on the motility of the isolated guinea-pig urinary bladder, ileum, colon and gall bladder. After decapitation of the animals, their smooth muscles were quickly removed and placed in a 10-ml organ bath (37°C) in Krebs solution (bubbled 95% 02, 5~; CO2) under a resting tension of 1 g. CAP (10 -5 M) produced a contraction in the urinary bladder. A second administration of CAP reduced the amplitude of contractions, indicating desensitization. CAP produced a concentration-dependent contraction on the ileal segments. Biphasic effects were observed on the colon; CAP caused a contraction in low doses (10 -7 M), but a relaxation in high dose (10 -5 M). Contractions occurred in the gall bladder but desensitization was not observed.
References Maggi, C.A. et al. Gen. Pharmac. 1988, 19 (1) 1-43. Santiciofi, P. et al. J. Urol. 1985, 133, 700-704. Sharkey, K.A. et aLl.Neuroscience 1983, 10, 861-86°.