Effects of 5-HT1A and 5-HT4 receptor agonists on slow synaptic potentials in enteric neurons.

Intracellular electrophysiological methods were used to examine the effects of 5-hydroxytryptamine (5-HT), 5-carboxamidotryptamine (5-CT), 5-methoxytryptamine (5-MeOT), 4-amino-5-chloro-2-methoxy-N-(4-[1-azabicyclo[3,3,1]nonyl]) benzamide hydrochloride (renzapride), cis-4-amino-5-chloro-N[1-[3- (4-fluorophenoxy)propyl]-3-methoxy-4-piperidinyl[-2-methoxybenzamide monohydrate (cisapride) and endo-N-(8-methyl-8-azabicyclo[3.2.1]oct-3-yl)-2,3-dihydro-3- (1-methyl)ethyl-2-oxo-1 H-benzimidazole-1-carboxamidehydrochloride (BIMU 8) on noncholineric slow excitatory postsynaptic potentials (slow EPSPs) in myenteric afterhyperpolarization (AH) neurons of guinea pig ileum. 5-HT (0.01-1 microM) and 5-CT (0.001-0.1 microM) produced a concentration-dependent inhibition of slow EPSPs. The 5-HT1A receptor antagonist 1-(2-methoxyphenyl)-4-[4-(2-phthalimidobutyl]piperazine (NAN-190) produced rightward shifts in 5-HT and 5-CT concentration-response curves; facilitation of slow EPSPs was never observed. 5-MeOT caused a depolarization and inhibited spike afterhyperpolarizations in a concentration-dependent manner but this effect was not blocked by the 5-HT3/5-HT4 receptor antagonist, tropisetron (1 microM). Renzapride (0.01-0.3 microM), cisapride (0.01-1.0 microM) and BIMU 8 (0.01-1.0 microM) did not change the membrane potential of any neuron tested. Renzapride and BIMU 8 did not change the amplitude of slow EPSPs. In 13 of 19 neurons cisapride did not change the amplitude of slow EPSPs; in 6 neurons cisapride (1 microM) reversibly inhibited the slow EPSP. Responses to substance P which mimicked the slow EPSP were not affected by cisapride.(ABSTRACT TRUNCATED AT 250 WORDS)