On the nature of the contractile motor responses of the rat stomach elicited by serotonin or substance P in vitro.

SP or 5-HT elicited contractile motor responses from strip preparations of the rat antrum and pylorus, effects which were efficiently antagonized by blockade directed against each substance (SP-receptors: tachyphylaxis or a SP analogue; 5-HT2 receptors: ketanserin). Indirect effects of SP or 5-HT, i.e. causing the release of other spasmogens such as histamine (from mast cells) and prostaglandins, were ruled out in separate experiments using pyrilamine or indomethacin. When the contractile effects of SP or 5-HT motor responses were studied after TTX no inhibition was demonstrated indicating that the effects were mediated via muscle receptors. Both SP- and 5-HT-responses were partially antagonized by blockade of muscarinic or nicotinic receptors, even in the presence of TTX, in favour of interaction at the receptor level of the smooth muscle membrane. One exception was the SP-induced pyloric contraction, which was partially atropine-sensitive but resistant to hexamethonium. Interestingly, blockade of 5-HT2 receptors (ketanserin) reduced the contractile response to SP. These observations indicate an interaction between SP and 5-HT receptors at the smooth muscle membrane. However, SP and 5-HT added together did no facilitate the response. Therefore, the interaction of ketanserin with the SP response may rather be sterical than due to binding to a common receptor site. These findings may be of importance, since SP and 5-HT have recently been shown to coexist in gut neurons.