Actions of serotonin and substance P on myenteric neurons of guinea-pig distal colon.

Intracellular methods were used to study the effects of serotonin and substance P (SP) on the electrical behavior of myenteric neurons in guinea-pig distal colon in vitro. Serotonin evoked either a short-duration transient depolarization, a long-lasting depolarization or a multiphasic response consisting of a rapid depolarization followed by a short duration hyperpolarizing potential and then a long-lasting depolarization. Application of SP evoked a long-lasting depolarization. Depolarizing potentials to both substances were accompanied by enhanced excitability that was reflected by repetitive spike discharge. Long-lasting depolarizations were associated with increased input resistance. The responses to serotonin or SP were unaltered by the presence of tetrodotoxin, hexamethonium or elevated extracellular Mg2+ and reduced Ca2+. Some neurons responded to both serotonin and SP indicating that both receptors coexisted on the same neuron. The putative SP antagonist, [D-Arg1,D-Phe5,D-Trp7,9,Leu11]SP did not affect the responses to SP. It did suppress the slow-depolarizing response to serotonin, while the fast response was unaffected. The responses to serotonin and SP in myenteric neurons of guinea-pig colon resembled the responses reported by others for small intestinal myenteric neurons.