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

Abstract

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.