Summary
The effects of 3′,5′-cyclic nucleotide phosphodiesterase (PDE) inhibitors and of 8-Br 3′,5′-cyclic nucleotide analogs on nerve-muscle transmission were studied in the guinea-pig vas deferens preincubated with 3H-noradrenaline.
8-Br cyclic AMP and the PDE inhibitors 3-isobutyl-1-methylxanthine (IBMX) and 3-propionyl-4-hydrazinopyrazolopyridine (SQ 20006) enhanced the secretion of 3H-NA evoked by transmural nerve stimulation. 8-Br cyclic GMP was without effect in this respect.
The muscle contraction evoked by transmural nerve stimulation, high potassium or by application of exogenous noradrenaline was depressed by IBMX and SQ 20006. The contraction evoked by transmural nerve stimulation was enhanced by 8-Br cyclic AMP and depressed by 8-Br cyclic GMP.
These findings suggest differential involvement of 3′,5′-adenosine- and guanosine-cyclic nucleotides in excitation-secretion-coupling in the noradrenergic sympathetic nerves, and in excitation-contraction-coupling in the smooth muscle, of guinea-pig vas deferens.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Bartfai, T.: Cyclic nucleotides in the central nervous system. Trends in Biochem. Sci. 3, 121–124 (1978)
Butcher, F. R., Rudich, L., Emler, C., Nemerovski, L.: Adrenergic regulation of cyclic nucleotide levels, amylase release, and potassium efflux in rat parotid gland. Mol. Pharmacol. 12, 862–870 (1976)
Cubeddu, L. X., Barnes, E., Weiner, N.: Release of norepinephrine and dopamine-β-hydroxylase by nerve stimulation. IV. An evaluation of a role for cyclic adenosine monophosphate. J. Pharmacol. Exp. Ther. 193, 105–127 (1975)
Fredholm, B. B., Hedqvist, P., Vernet, L.: Effects of theophylline and related compounds on rabbit renal cyclic nucleotide phosphodiesterase, 5′-nucleotidase and adenosine deaminase. Biochem. Pharmacol. 27, 2845–2850 (1978)
Heersche, J. N. M., Ferak, S. A., Aurbach, J. D.: The mode of action of dibutyryl adenosine 3′,5′-monophosphate in bone tissue in vitro. J. Biol. Chem. 246, 6770–6775 (1971)
Hughes, J.: Differential labelling of intraneuronal noradrenaline stores with different concentrations of (-)-3H-noradrenaline. Br. J. Pharmacol. 47, 428–430 (1973)
Langer, S. X.: Sixth Gaddum Memorial Lecture, National Institute for Medical Research, Mill Hill, January 1977: Presynaptic receptors and their role in the regulation of transmitter release. Br. J. Pharmacol. 60, 481–497 (1977)
Langer, S. Z., Adler-Graschinsky, E., Enero, M. A.: Positive feedback mechanisms for the regulation of noradrenaline released by nerve stimulation. Abstr. of Jerusalem Satellite Symp. XXVI Int. Congr. of Physiol. Sci., p. 81 (1974)
Mannervik, B., Bartfai, T.: Discrimination between mathematical models of biological systems exemplified by enzyme steady state kinetics. Acta Biol. Med. Germ. 31, 203–215 (1973)
O'Dea, R. F., Zatz, M.: Catecholamine-stimulated cyclic GMP accumulation in the rat pineal: Apparent presynaptic site of action. Proc. Natl. Acad. Sci. USA 73, 3398–3402 (1976)
Pelayo, F., Dubocovich, M. L., Langer, S. Z.: Possible role of cyclic nucleotides in regulation of noradrenaline release from rat pineal through presynaptic adrenoceptors. Nature 274, 76–78 (1978)
Robison, G. A., Butcher, R. W., Sutherland, E. W.: Cyclic AMP. New York, London: Academic Press 1971
Schultz, K.-D., Böhme, E., Kreye, V. A. W., Schultz, G.: Relaxation of hormonally stimulated smooth muscular tissues by the 8-bromo derivative of cyclic GMP. Naunyn-Schmiedeberg's Arch. Pharmacol. 306, 1–9 (1979)
Starke, K.: Regulation of noradrenaline release by presynaptic receptor systems. Rev. Physiol. Biochem. Pharmacol. 77, 1–124 (1977)
Stjärne, L.: Basic mechanisms and local feedback control of secretion of adrenergic and cholinergic neurotransmitters. In: Handbook of psychopharmacology, Vol. 6 (L. L. Iversen, S. D. Iversen and S. H. Snyder, eds.), pp. 179–233. New York: Plenum Publ. Co. 1975
Stjärne, L.: Relative importance of calcium and cyclic AMP for noradrenaline secretion from sympathetic nerves of guinea-pig vas deferens and for prostaglandin induced depression of noradrenaline secretion. Neuroscience 1, 19–22 (1976)
Stjärne, L.: Role of prostaglandins and cyclic adenosine monophosphate in release. In: The release of catecholamines from adrenergic neurons (D. M. Paton, ed.), pp. 111–142. Oxford, New York: Pergamon Press 1978a
Stjärne, L.: Inhibitory effects of noradrenaline and prostaglandin E2 on neurotransmitter secretion evoked by single shocks or by short trains of nerve stimuli. Acta Physiol. Scand. 102, 251–253 (1978b)
Stjärne, L.: The dependence of the presynaptic control of noradrenaline secretion on train length and frequency of nerve stimulation. In: Presynaptic receptors (S. Z. Langer, K. Starke and M. L. Dubocovich, eds.). Oxford: Pergamon Press (in press, 1979)
Stjärne, L., Brundin, J.: Dual adrenoceptor mediated control of noradrenaline secretion from human vasoconstrictor nerves: Facilitation by β-adrenoceptors and inhibition by α-adrenoceptors. Acta Physiol. Scand. 94, 139–141 (1975)
Stjärne, L., Alberts, P., Bartfai, T.: Models of regulation of norepinephrine secretion by prejunctional receptors and by facilitation: Role of calcium and cyclic nucleotides. In: Catecholamines: Basic and clinical frontiers (E. Usdin, I. J. Kopin and J. Barchas, eds.). Oxford: Pergamon Press (in press, 1979)
Westfall, T. C.: Local regulation of adrenergic neurotransmission. Physiol. Rev. 57, 659–728 (1977)
Wooten, G. F., Thoa, N. B., Kopin, I. J., Axelrod, J.: Enhanced release of dopamine β-hydroxylase and norepinephrine from sympathetic nerves by dibutyryl cyclic adenosine 3′,5′-monophosphate and theophylline. Mol. Pharmacol. 9, 178–183 (1973)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Stjärne, L., Bartfai, T. & Alberts, P. The influence of 8-Br 3′,5′-cyclic nucleotide analogs and of inhibitors of 3′,5′-cyclic nucleotide phosphodiesterase, on noradrenaline secretion and neuromuscular transmission in guinea-pig vas deferens. Naunyn-Schmiedeberg's Arch. Pharmacol. 308, 99–105 (1979). https://doi.org/10.1007/BF00499050
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00499050