5-HT1A receptor-mediated inhibition of acetylcholine release from guinea pig myenteric plexus: Potential mechanisms

The mechanisms through which presynaptic 5-HT1A receptors cause inhibition of acetylcholine release from the guinea pig myenteric plexus were investigated. The selective 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) and 5-hydroxytryptamine (5-HT) caused concentration-dependent inhibitions of the electrically evoked release of [H-3]acetylcholine from myenteric plexus preparations that had been preincubated with [H-3]choline. The inhibitory effects were not modified by the activator of adenylyl cyclase, forskolin (10 mu M), the phosphodiesterase inhibitor, AH 21-132 (100 mu M), or after pretreatment of the guinea pigs with pertussis toxin (60 mu g/kg). In contrast, the protein kinase C activator 4 beta-phorbol-12,13-dibutyrate (0.1 mu M) prevented the release-inhibiting effect of 8-OH-DPAT, whereas the inactive isomer 4 alpha-phorbol-12,13-dibutyrate (0.1 mu M) was without effect. The results suggest that the presynaptic 5-HT1A receptor is not coupled to a pertussis toxin sensitive G protein or to adenylyl cyclase. However, protein kinase C seems to be involved in the mechanism of inhibition of acetylcholine release by presynaptic 5-HT1A receptors. (C) 1996 Elsevier Science Ltd.