Involvement of 5-HT3 and 5-HT4 receptors in the motor activity of isolatedvascularly perfused rat duodenum

The involvement of serotonin (5-HT) receptor subtypes in motor activity of the ex vivo vascularly perfused rat duodenum was investigated. Clusters of phasic contractions (CPCs), migrating in an oral to anal direction, were ob tained without any stimulation. Drug effects were evaluated by changes in d ifferent components of the pressure waves, such as motor index (MI), freque ncy, amplitude and duration of the CPC. The effect of 5-HT depletion on mot or activity was examined in animals treated with p-chlorophenylalanine (PCP A). The MI, frequency and duration of CPC were decreased by PCPA, but the a mplitude was not affected, suggesting that endogenous 5-HT may play an impo rtant role in regulation of the motor activity of the rat intestine. The im portance of the 5-HT receptor subtypes in the regulation of motor activity was examined. Neither the nonselective 5-HT1 and 5-HT2 receptor antagonist, methysergide, nor the 5-HT2 receptor antagonist, ketanserin, affected moto r activity. However, the 5-HT3 receptor antagonists, granisetron and azaset ron, decreased percentage MI, frequency, percentage amplitude and percentag e duration of CPC. The 5-HT4 receptor antagonist, SB204070, exerted both ex citatory and inhibitory actions, with a higher dose (10 nM) stimulating per centage MI, frequency, percentage amplitude and percentage duration, and a lower dose (0.1 nM or 1 nM) decreasing percentage MI and percentage duratio n of CPC. These results suggest that endogenous 5-HT regulates the motor ac tivity of the rat duodenum through 5-HT3 and 5-HT4 receptors, with the form er mediating the stimulatory influence and the latter mediating both stimul atory and inhibitory influences.