Effects of oxotremorine and RMI 12330 A on [3H]acetylcholine release and adenylate cyclase activity in guinea pig superior cervical ganglion

Abstract

There is considerable evidence that adenosine 3',5'-cyclic monophosphate (cAMP) is involved in the modulation of synaptic transmission in the guinea pig superior cervical ganglion (SCG). Presynaptic muscarinic receptors are known to attenuate, when activated, acetylcholine (ACh) release in the periphery as well as in the brain. Thus, the possible relationship between ganglionic adenylate cyclase activity and the output of ACh from electrically stimulated ganglia, preloaded with [3H]choline, was investigated. The muscarinic agonist oxotremorine significantly reduced in a dose-dependent manner the electrically evoked neurotransmitter release. The adenylate cyclase inhibitor N-(cis-2-phenylcyclopentyl)azacyclotridecan-2-imine hydrochloride (RMI 12330 A) also decreased ACh output. The inhibitory effects of these two drugs were additive. In crude ganglion membrane fractions oxotremorine significantly inhibited adenylate cyclase activity. The results indicate that drugs capable of inhibiting adenylate cyclase, significantly decrease ACh output from preganglionic nerve terminals in guinea pig SCG.

Presynaptic muscarinic inhibition in bullfrog sympathetic ganglia.

“…A similar negative conclusion was reached concerning the parasympathetic pelvic ganglion in the rat (Somogyi & DeGroat, 1993). On the other hand, evidence in favour of presynaptic muscarinic receptors in sympathetic ganglia has been obtained in collection experiments on the guineapig SCG (Capuzzo, Borasio & Fabbri, 1988, 1989) and cat stellate ganglion (Dujic, Roerig, Schedewie, Kampine & Bosnjak, 1990). These contradictory conclusions cannot be explained simply by differences in species or preparations because recent work has provided positive evidence for presynaptic muscarinic inhibition in the cat SCG (Bachoo & Polosa, 1992).…”