Abstract
The aim of the present study was to clarify whether cotinine affects the release of catecholamines (CA) from the isolated perfused rat adrenal gland, and to establish the mechanism of its action, in comparison with the response of nicotine. Cotinine (0.3~3 mM), when perfused into an adrenal vein for 60 min, inhibited CA secretory responses evoked by ACh (5.32 mM), DMPP (a selective neuronal nicotinic agonist, 100 μM for 2 min) and McN-A-343 (a selective muscarinic M1agonist, 100 μM for 2 min) in dose- and time-dependent manners. However, cotinine did not affect CA secretion by high K+ (56 mM). Cotinine itself also failed to affect basal CA output. Furthermore, in the presence of cotinine (1 mM), CA secretory responses evoked by Bay-K-8644 (an activator of L-type Ca2+ channels, 10 μM) and cyclopiazonic acid (an inhibitor of cytoplasmic Ca2+-ATPase, 10 μM) were relative time-dependently attenuated. However, nicotine (30 μM), given into the adrenal gland for 60 min, initially rather enhanced CA secretory responses evoked by ACh and high K+, followed by the inhibition later, while it time-dependently depressed the CA release evoked by McN-A-343 and DMPP. Taken together, these results suggest that cotinine inhibits greatly CA secretion evoked by stimulation of cholinergic (both nicotinic and muscarinic) receptors, but does fail to affect that by the direct membrane-depolarization. It seems that this inhibitory effect of cotinine may be exerted by the cholinergic blockade, which is associated with blocking both the calcium influx into the rat adrenal medullary chromaffin cells and Ca2+ release from the cytoplasmic calcium store. It also seems that there is a big difference in the mode of action between cotinine and nicotine in the rat adrenomedullary CA secretion.
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References
Akaike, A., Mine, Y., Sasa, M., and Takaori, S., Voltage and current clamp studies of muscarinic and nicotinic excitation of the rat adrenal chromaffin cells.J. Pharmacol. Expt. Ther., 255, 333–339 (1990).
Andersson, K., Jansson, A., Kuylenstierna, F., and Eneroth, P., Nicotine and its major metabolite cotinine have different effects on aldosterone and prolactin serum levels in he normal male rat.Eur. J. Pharmacol., 228, 305–312 (1993).
Anton, A. H. and Sayre, D. F., A study of the factors affecting the aluminum oxidetrihydroxy insole procedure for the analysis of catecholamines.J. Pharmacol. Exp. Ther., 138, 360–375 (1962).
Benowitz, N. L., Jacob, P., Pong, I., and Gupta, S., Nicotine metabolic profile in man: Comparison of cigarette smoking and transdermal nicotine.J. Pharmacol. Exp. Ther., 268, 296–303 (1994).
Benowitz, N. L. and Jacob, P., Pharmacokinetics and metabolism of nicotine and related alkaloids: In Arneric, S.P. and Brioni, J.D. (Eds.). Neuronal Nicotinic Receptors. Pharmacology and Therapeutic Opportunities, Wiley-Liss, New York, pp. 213–234, (1999).
Benowitz, N. L., Kuyt, F., Jacob, P., Jones, R. T., and Osman, A. L., Cotinine disposition and effects.Clin. Pharmacol. Ther., 34, 604–611 (1983).
Borzelleca, J. F., Bowman, E. R., and McKennis, H. Jr., Studies on the respiratory and cardiovascular effects of (−)-cotinine.J. Pharmacol. Exp. Ther., 137, 313–318 (1962).
Chahine, R., Aftimos, G., Wainberg, M. C., Navarro-Delmasure, C., Abou Khalil, K., and Chahoud, B., Cotinine modulates the cardiovascular effects of nicotine.Med. Sci. Res., 24, 21–23 (1996).
Chahine, R., Calderone, A., and Navarro-Delmasure, C., Thein vitro effects of nicotine and cotinine on prostacyclin and thromboxane biosynthesis.Prostaglandins Leukot Essent Fatty Acids, 40, 261–266 (1990).
Challiss, R. A. J., Jones, J. A., Owen, P. J., and Boarder, M. R., Changes in inositol 1,4,5-trisphosphate and inositol 1,3,4,5-tetrakisphosphate mass accumulations in cultured adrenal chromaffin cells in response to bradykinin and histamine.J. Neurochem., 56, 1083–1086 (1991).
Cheek, T. R., O’Sullivan, A. J., Moreton, R. B., Berridge, M. J., and Burgoyne, R. D., Spatial localization of the stimulus-induced rise in cyrosolic Ca2+ in bovine adrenal chromaffin cells: Distinct nicotinic and muscarinic patterns.FEBS Lett., 247, 429–434 (1989).
Crooks, P. A., Li, M., and Dwoskin, L. P., Metabolites of nicotine in rat brain after peripheral nicotine administration: Cotinine nornicotine and norcotinine.Drug Metab. Dispos., 25, 47–54 (1997).
Cryer, P. E., Haymond, M. W., Santiago, J. V., and Shah, S. D., Norepinephrine and epinephrine release and adrenergic mediation of smoking associated hemodynamic and metabolic events.N. Engl. J. Med., 295, 573–577 (1976).
Dar, M. S., Bowman, E. R., and Li, C., Intracerebellar nicotinic-cholinergic participation in the cerebella adesinoergic modulation of ethanol-induced motor incoordination in mice.Brain Res., 644, 117–127 (1994).
Douglas, W. W., Kanno, and Sampson, S. R., Influence of the ionic environment on the membrane potential of adrenal chromaffin cells and on the depolarizing effect of acetylcholine.J. Physiol., 191, 107–121 (1967).
Douglas, W. W. and Rubin, R. P., The role of calcium in the secretary response of the adrenal medulla to acetylcholine.J. Physiol., 159, 40–57 (1961).
Dwoskin, L. P., Teng, L., Buxton, S. T., and Crooks, P. A., S-(−)-Cotinine, the major brain metabolite of nicotine, stimulates nicotinic receptors to evoke [3H] dopamine release from rat striatal slices in acalcium-dependent manner.J. Pharmacol. Exp. Ther., 288, 905–911 (1999).
Erenmemisoglu, A. and Tekol, Y., Do nicotine metabolites have an effect on pain perception? Antinociceptive effect of cotinine in mice.Pharmazie, 49, 374–375 (1994).
Garcia, A. G., Sala, F., Reig, J. A., Viniegra, S., Frias, J., Ronteriz, R., and Gandia, L., Ihydropyridine Bay-K-8644 activates chromaffin cell calcium channels.Nature, 309, 69–71 (1984).
Garvey, A. J., Ward, K. D., Bliss, R. E., Rosner, B., and Vokonas, P. S., Relation between saliva cotinine concentration, cigarette consumption, and blood pressure among smokers.Am. J. cardiol., 76(1), 95–97 (1995).
Goeger, D. E. and Riley, R. T., Interaction of cyclopiazonic acid with rat skeletal muscle sarcoplasmic reticulum vesicles. Effect on Ca2+ binding and Ca2+ permeability.Biochem. Pharmacol., 38, 3995–4003 (1989).
Goldberg, S. R., Risner, M. E., Stolerman, I. P., Reavill, C., and Garcha, H. S., Nicotine and some related compounds: effects on schedule-controlled behavior and discriminative properties in rats.Psycho. pharmacology, 97, 265–302 (1989).
Gorrod, J. W. and Wahren, J., Nicotine and Related Alkaloids: Absorption, Distribution, Metabolism, Excretion. Chapman and Hall, London, (1993).
Hammer, R. and Giachetti, A., Muscarinic receptor subtypes: M1 and M2 biochemical and functional characterization.Life Sci., 31, 2992–2998 (1982).
Hatsukami, D. K., Grillo, M., Pentel, P. R., Oncken, C., and Bliss, R., Safety of cotinine in humans: physiologic, subjective and cognitive effects.Pharmacol. Biochem. Behav., 57, 643–650 (1997).
Hatsukami, D., Pentel, P. R., Jensen, J., Nelson, D., Allen, S. S., Goldman, A., and Rafael, D., Cotinine: effects with and without nicotine.Psychopharmacology, 135, 141–150 (1998).
Hurt, R. D., Dale, L. C., Offord, K. P., Lauger, G. G., Baskin, L. B., Lawson, G. M., Jiang, N. S., and Hauri, P. J., Serum nicotine and cotinine levels during nicotine-patch therapy.Clin. Pharmacol. Ther., 54, 98–106 (1993).
lino, M., Calcium-induced calcium release mechanism in guinea pig taenia caeci.J. Gen. Physiol., 94, 363–383 (1989).
Keenan, R. M., Hatsukami, D. K., Pentel, P. R., Thompson, T. N., and Grillo, M. A., Pharmacodynamic effects of cotinine in abstinent cigarette smokers.Clin. Pharmacol. Ther., 55, 581–590 (1994).
Kilpatrick, D. L., Slepetis, R., and Kirshner, N., Ion channels and membrane potential in stimulus-secretion coupling in adrenal medulla cells.J. Neurochem., 36, 1245–1255 (1981).
Kim, K. S., Borzelleca, J. F., Bowman, E. R., and McKennis, H. Jr., Effects of some nicotine metabolites and related compounds on isolated smooth muscle.J. Pharmacol. Exp. Ther., 161, 59–69 (1968).
Ladona, M. G., Aunis, D., Gandia, A. G., and Garcia, A. G., Dihydropyridine modulation of the chromaffin cell secretory response.J. Neurochemstry, 48, 483–490 (1987).
Lim, D. Y. and Hwang, D.-H., Studies on secretion of catecholamines evoked by DMPP and McN-A-343 in the rat adrenal gland.Kor. J. Pharmacol., 27(1), 53–67 (1991).
Lim, D. Y., Kim, C.-D., and Ahn, K.-W., Influence of TMB-8 on secretion of catecholamines from the perfused rat adrenal glands.Arch. Pharm. Res., 15(2), 115–125 (1992).
Oka, M., Isosaki, M. and Yanagihara, N., Isolated bovine adrenal medullary cells: studies on regulation of catecholamine synthesis and release: In Catecholamines: Basic and Clinical frontiers (Eds. Usdin, E., Kopin, I. J., and Brachas, J.). Pergamon Press, Oxford, pp. 70–72, (1979).
Patterson, T. R., Stringham, J. D., and Meikle, A. W., Nicotine and cotinine inhibit steroidogenesis in mouse Leydig cells.Life Sci., 46, 265–272 (1990).
Pinto, J. E. B. and Trifaro, J. M., The different effects of D-600 (methoxyverapamil) on the release of adrenal catecholamines induced by acetylcholine, high potassium or sodium deprivation.Brit. J. Pharmacol., 57, 127–132 (1976).
Saareks, V., Riutta, A., Mucha, I., Alanko, J., and Vapaatalo, H., Nicotine and cotinine modulate eicosanoid production in human leukocytes and platelet rich plasma.Eur. J. Pharmacol., 248(4), 345–349 (1993).
Sastry, B. V. R., Chance, M. B., Singh, G., Horn, J. L., and Janson, V. E., Distribution and retention of nicotine and its metabolite, cotinine, in the rat as a function of time.Pharmacology, 50, 128–136 (1995).
Schramm, M., Thomas, G., Towart, R., and Franckowiak, G., Novel dihydropyridines with positive isotropic action through activation of Ca2+ channels.Nature, 303, 535–537 (1982).
Seidler, N. W., Jona, I., Vegh, N., and Martonosi, A., Cyclopiazonic acid is a specific inhibitor of the Ca2+-ATPase of sarcoplasimc reticulum.J. Biol. Chem., 264, 17816–17823 (1989).
Shoaib, M. and Stolerman, I. P., Plasma nicotine and cotinine levels following intravenous nicotine self-administration in rats.Psychopharmacology, (Berl) 143(3), 318–321 (1999).
Suzuki, M., Muraki, K., Imaizumi, Y., and Watanabe, M., Cyclopiazonic acid, an inhibitor of the sarcoplasmic reticulum Ca2+-pump, reduces Ca2+-dependent K+ currents in guinea-pig smooth muscle cells.Br. J. Pharmacol., 107, 134–140 (1992).
Takada, K., Swedberg, M. D., Goldberg, S. R., and Katz, J. L., Discriminative stimulus effects effects of intravenous 1-nicotine analogs or metabolites in squirrel monkeys.Psycho. pharmacology, 99, 208–212 (1989).
Tallarida, R. J. and Murray, R. B., Manual of pharmacologic calculation with computer programs. 2nd Ed New York Speringer-Verlag, pp. 132, (1987).
Uceda, G., Artalejo, A. R., Lopez, M. G., Abad, F., Neher, E., and Garcia, A. G., Ca2+-activated K+ channels modulated muscarinic secretion in ca chromaffin cells.J. Physical., 454, 213–230 (1992).
Uyama, Y., Imaizumi, Y., and Watanabe, M., Effects of cyclopiazonic acid, a novel Ca2+-ATPase inhibitor on contractile responses in skinned ideal smooth muscle.Br. J. Pharmacol., 106, 208–214 (1992).
Vainio, P. J., Vilusksela, M., and Tuominen, R. K., Inhibition of nicotinic by cotinine in bovine adrenal chromaffin cells.Pharmacol. Toxical., 83, 188–193 (1998).
Wada, Y., Satoh, K., and Taira, N., Cardiovascular profile of Bay-K-8644, a presumed calcium channel activator in the dog.Naunyn-Schmiedebergs Arch. Pharmacol., 328, 382–387 (1985).
Wakade, A. R., Studies on secretion of catecholamines evoked by acetylcholine or transmural stimulation of the rat adrenal gland.J. Physiol., 313, 463–480 (1981).
Winders, S. E., Grunberg, N. E., Benowitz, N. L., and Alvares, A. P., Effects of stress on circulating nicotine and cotinine levels andin vitro nicotine metabolism in the rat.Psychopharmacology, 137, 383–390 (1998).
Yeh, J., Barbieri, R. J., and Friedman, A. J., Nicotine and cotinine inhibit rat testes androgen biosynthesisin vitro.Steroid Biochem., 33, 627–630 (1989).
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Koh, YY., Jang, SJ. & Lim, DY. Cotinine inhibits catecholamine release evoked by cholinergic stimulation from the rat adrenal medulla. Arch Pharm Res 26, 747–755 (2003). https://doi.org/10.1007/BF02976686
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DOI: https://doi.org/10.1007/BF02976686