Summary
Injections of guanylyl-imido-diphosphate (250, 500 and 1,000 μg/kg) into the lateral cerebral ventricle of the anaesthetized cat induced increases in blood pressure and heart rate while the intravenous injections of the same doses were ineffective, thus indicating a central mechanism of action of this compound which activates adenylcyclase at the catalytic subunit. The results support the hypothesis that the activity of cardiovascular centres depends on the prevailing concentration of cAMP.
Intracerebroventricular injection of cGMP (125, 250 and 500 μg/kg) caused hypotension and bradycardia. The effects increased with the dose but were subject to tachyphylaxis. The lack of an effect after intravenous administration indicates a central site of action. This result is in agreement with the Yin Yang hypothesis and suggests that cGMP is a second transmitter in cardiovascular centres which may be involved in central cardiovascular effects in response to stimulation by putative neurotransmitter substances such as acetylcholine.
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Antilla, P., Lücke, C., Westermann, E.: Stimulation of adenylate cyclase of guinea pig gastric mucosa by histamine, sodium fluoride and 5′-guanylylimido-diphosphate and inhibition by histamine H1- and H2-receptors antagonists in vitro. Naunyn-Schmiedeberg's Arch. Pharmacol. 296, 31–36 (1976)
Brezenoff, H. E., Jenden, D. J.: Changes in arterial blood pressure after microinjections of carbachol into the medulla and IV-th ventricle of the rat brain. Neuropharmacol. 9, 341–348 (1970)
Clipsham, P. J., Hamilton, T. C., Hunt, A. A. E., Poyser, R. H.: Cyclic nucleotides and central cardiovascular control in the cat. Br. J. Pharmacol. 64, 395P (1978)
Day, M. D., Roach, A. G.: Central α- and β-adrenoceptors modifying arterial blood pressure and heart rate in conscious cats. Br. J. Pharmacol. 51, 325–333 (1974)
Delbarre, B., Senon, D., Schmitt, H.: Study on the cardiovascular action of dibutyryl-3′,5′-cyclic AMP (DBcAMP) following the intraventricular administration to cats. Sixth International Congress of Pharmacology, Helsinki, Finland, 1975. Abstract No. 516
Delbarre, B., Senon, D., Schmitt, H.: Cyclic 3′,5′-adenosine monophosphate and central circulatory control in cats and dogs. Clin. Exp. Pharmacol. Physiol. 4, 341–348 (1977)
Dinnendahl, V., Stock, K.: Effects of arecoline and cholinesterase inhibitors on cGMP and cAMP in mouse brain. Naunyn-Schmiedeberg's Arch. Pharmacol. 290, 297–306 (1975)
Ferrendelli, J. A., Steiner, A. L., McDougal, D. B., Kipnis, D. M.: The effect of oxotremorine and atropine on cGMP and cAMP levels in mouse cerebral cortex and cerebellum. Biochem. Biophys. Res. Commun. 41, 1061–1067 (1970)
Ferrendelli, J. A., Kinscherf, D. A., Kipnis, D. M.: Effects of amphetamine, chlorpromazine and reserpine on cyclic GMP and cyclic AMP levels in mouse cerebellum. Biochem. Biophys. Res. Commun. 46, 2114–2120 (1972)
Ferrendelli, J. A., Kinscherf, D. A., Chang, M. M.: Regulation of levels of cGMP in the central nervous system: effects of depolarizing agents. Mol. Pharmacol. 9, 445–454 (1973)
Finch, L., Hicks, P. E.: Central hypertensive action of histamine in conscious normotensive cats. Eur. J. Pharmacol. 36, 263–266 (1976)
Finch, L., Hicks, P. E.: Involvement of hypothalamic histaminereceptors in the central cardiovascular actions of histamine. Neuropharmacol 16, 211–218 (1977)
Goldberg, N. D., Haddox, M. K., Hartle, D. K., Hadden, J. W.: The biological role of cyclic 3′,5′-guanosine monophosphate. In: Pharmacology and future of man. Proc. 5th Int. Congr. Pharmacology, San Francisco 1972, Vol. 5, pp. 146–169. Basel: Karger 1973a
Goldberg, N. D., O'Dea, R. F., Haddox, M. K.: Cyclic GMP. In: Advances in cyclic nucleotide research, Vol. 3 (P. Greengard, G. A. Robison, eds.), pp. 155–223. New York: Raven Press 1973b
Goldberg, N. D., Haddox, M. K., Nicol, S. E., Glass, D. B., Sanford, C. H., Kuehl, F. A., Estensen, R.: Biologic regulation through opposing influence of cGMP and cAMP: The Yin Yang hypothesis. In: Advances in cyclic nucleotide research, Vol. 5 (P. Greengard, G. A. Robison, eds.), pp. 307–330. New York: Raven Press 1975
Greengard, P., Kebabian, J. W.: Role of cAMP in synaptic transmission in the mammalian peripheral nervous system. Fed. Proc. 33, 1059–1068 (1974)
Hoffmann, W. E., Phillips, M. I.: A pressor response to intraventricular injections of carbachol. Brain Res. 105, 157–162 (1976)
Kobinger, W., Walland, A., Kadatz, R.: Stimulation of sympathetic cardiovascular centres by RA 642, a new pyrimido-pyrimidine derivative. Naunyn-Schmiedeberg's Arch. Pharmacol. 292, 105–111 (1976)
Kuo, J. F., Greengard, P.: Cyclic nucleotide-dependent protein kinases. IV. Isolation and partial purification of a protein kinase activated by cGMP. J. Biol. Chem. 245, 2493–2498 (1970)
Lang, W. J., Rush, M. L.: Cardiovascular responses to injections of cholinomimetic drugs into the cerebral ventricles of unanaesthetized dogs. Br. J. Pharmacol. 47, 196–205 (1973)
Lee, T. P., Kuo, J. F., Greengard, P.: Role of muscarinic cholinergic receptors in regulation of cGMP content in mammalian brain, heart muscle and intestinal smooth muscle. Proc. Natl. Acad. Sci. USA 69, 3287–3289 (1972)
Lefkowitz, R. J., Caron, M. G.: Characteristics of 5′-guanylylimidodiphosphate-activated adenylate cyclase. J. Biol. Chem. 205, 4418–4422 (1975)
Londos, C., Salomon, Y., Lin, M. C., Harwood, J. P., Schramm, M., Wolf, J., Rodbell, M.: 5′-guanylylimidodiphosphate, a potent activator of adenylate cyclase systems in eukariotic cells. Proc. Natl. Acad. Sci. USA 71, 3087–3090 (1974)
McAfee, D. A., Greengard, P.: cAMP: electrophysiological evidence for a role in synaptic transmission. Science 178, 310–312 (1972)
Nathanson, J. A.: Cyclic nucleotides and nervous system function. Physiol. Rev. 57, 157–256 (1977)
Phillis, J. W.: Evidence for cholinergic transmission in the cerebral cortex. Adv. Beh. Biol. 10, 57–80 (1974)
Porsius, A. J., Van Zwieten, P. A.: Central action of some cholinergic drugs (arecaidine esters) and nicotine on blood pressure and heart rate of cats. In: Progress in brain research. Hypertension and brain mechanisms, Vol. 47 (W. De Young, A. P. Provoost, A. P. Shapiro, eds.), pp. 131–135. Amsterdam: Elsevier 1977
Saxena, P. R., Bhargava, K. P.: Central beta-adrenoceptor sites and ouabian action. Pharmacol. Res. Commun. 6, 347–355 (1974)
Schramm, M., Rodbell, M.: A persistent active state of the adenylate cyclase system produced by combined actions of isoproterenol and guanylyl-imidophosphate in frog erythrocyte membranes. J. Biol. Chem. 250, 2232–2237 (1975)
Sinha, J. N., Dhawan, K. N., Chandra, O., Gupta, G. P.: Role of acetylcholine in central vasomotor regulation. Can. J. Physiol. Pharmacol. 45, 503–507 (1967)
Sinha, J. N., Gupta, M. L., Bhargava, K. P.: Effect of histamine and antihistaminics on central vasomotor loci. Eur. J. Pharmacol. 5, 235–238 (1969)
Snider, R. S., Niemer, W. T.: Stereotaxic atlas of the cat brain. Chicago: University of Chicago Press 1964
Stone, T. W., Taylor, D. A., Bloom, F. E.: cAMP and cGMP may mediate opposite neuronal responses in the rat cerebral cortex. Science 187, 845–847 (1975)
Trendelenburg, U.: Stimulation of sympathetic centres by histamine. Circ. Res. 5, 105–110 (1957)
Walland, A.: cAMP as a second messenger in central blood pressure control. Naunyn-Schmiedeberg's Arch. Pharmacol. 90, 419–423 (1975)
Walland, A.: Further evidence for the involvement of cAMP in central blood pressure regulation. Naunyn-Schmiedeberg's Arch. Pharmacol. 296, 177–181 (1977)
Walland, A., Schuhmacher, P.: Central modulation of vagal bradycardiac reflexes by cyclic nucleotides. In: Nervous system and hypertension, (P. Meyer, H. Schmitt, eds.), pp. 219–222. Paris: Flammarion 1979
Weiss, B.: On the regulation of adenyl cyclase activity in the rat pineal gland. Ann. N.Y. Acad. Sci. 185, 507–519 (1971)
White, T.: Some effects of histamine and two histamine metabolites on the cats brain. J. Physiol. (Lond.) 159, 198–202 (1961)
De Wildt, D. J., Porsius, A. J.: Central action of the cholinesterase inhibitor physostigmine on blood pressure and heart rate. Therapiewoche 27, 7795 (1977)
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Present address: Pharmakologisches Institut der Universität Düsseldorf, Universitätsstr. 1, D-4000 Düsseldorf, Federal Republic of Germany
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Schuhmacher, P., Walland, A. Central blood pressure effects of guanylyl-imido-diphosphate and cyclic guanosine-monophosphate. Naunyn-Schmiedeberg's Arch. Pharmacol. 312, 31–35 (1980). https://doi.org/10.1007/BF00502571
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DOI: https://doi.org/10.1007/BF00502571