5-HT1A, SST1, and SST2 receptors mediate inhibitory postsynaptic potentials in the submucous plexus of the guinea pig ileum

Foong JPP, Parry LJ, Gwynne RM, Bornstein JC. 5-HT1A, SST1, and SST2 receptors mediate inhibitory postsynaptic potentials in the submucous plexus of the guinea pig ileum. Am J Physiol Gastrointest Liver Physiol 298: G384-G394, 2010. First published December 10, 2009; doi: 10.1152/ajpgi.00438.2009.-Vasoactive intestinal peptide ( VIP) immunoreactive neurons are important secretomotor neurons in the submucous plexus. They are the only submucosal neurons to receive inhibitory inputs and exhibit both noradrenergic and nonadrenergic inhibitory synaptic potentials (IPSPs). The former are mediated by alpha(2)-adrenoceptors, but the receptors mediating the latter have not been identified. We used standard intracellular recording, RTPCR, and confocal microscopy to test whether 5-HT1A, SST1, and/or SST2 receptors mediate nonadrenergic IPSPs in VIP submucosal neurons in guinea pig ileum in vitro. The specific 5-HT1A receptor antagonist WAY 100135 (1 mu M) reduced the amplitude of IPSPs, an effect that persisted in the presence of the alpha(2)-adrenoceptor antagonist idazoxan (2 mu M), suggesting that 5-HT might mediate a component of the IPSPs. Confocal microscopy revealed that there were many 5-HT-immunoreactive varicosities in close contact with VIP neurons. The specific SSTR2 antagonist CYN 154806 (100 nM) and a specific SSTR1 antagonist SRA 880 (3 mu M) each reduced the amplitude of nonadrenergic IPSPs and hyperpolarizations evoked by somatostatin. In contrast with the other antagonists, CYN 154806 also reduced the durations of nonadrenergic IPSPs. Effects of WAY 100135 and CYN 154806 were additive. RT-PCR revealed gene transcripts for 5-HT1A, SST1, and SST2 receptors in stripped submucous plexus preparations consistent with the pharmacological data. Although the involvement of other neurotransmitters or receptors cannot be excluded, we conclude that 5-HT1A, SST1, and SST2 receptors mediate nonadrenergic IPSPs in the noncholinergic (VIP) secretomotor neurons. This study thus provides the tools to identify functions of enteric neural pathways that inhibit secretomotor reflexes.