Effects of 5-hydroxytryptamine on the transintestinal electrical activity and cardiovascular function of fawn-hooded...

Fawn-hooded rats, which have abnormal serotonergic function, were used to investigate the receptors involved in 5-hydroxytryptamine (5-HT)-induced intestinal secretion. The effects of 5-HT on secretion by the small intestine and proximal colon, monitored as increased transintestinal electrical activity, and on cardiovascular function, measured as changes in heart rate and blood pressure, were compared in fawn-hooded and Wistar rats. The maximum fall in heart rate induced by 5-HT (mediated by 5-HT3 receptors) was greater in fawn-hooded than in Wistar rats. ED50 values (the doses resulting in 50% of the maximum effect) for the 5-HT2-mediated increases in systolic pressure were lower for both 5-HT and 5-methoxytryptamine in the fawn-hooded group. The prolonged fall in diastolic pressure mediated by 5-HT1-like receptors was significantly attenuated in fawn-hooded rats, with the maximum responses to 5-HT, 5-methoxytryptamine and 6-hydroxyindalpine reduced to 21%, 42% and 28%, respectively, of the values obtained for Wistar rats. In fawn-hooded rats the small intestine was less sensitive to the effects of 5-HT (ED50 = 47 nmol kg(-1); ED50 for Wistar rats = 23 nmol kg(-1)) and the maximum colonic response to 5-methoxytryptamine was greater (7.0 mV compared with 4.3 mV in Wistar rats), but other indices did not differ for the two strains. The responses to 6-hydroxyindalpine were similar in fawn-hooded and Wistar rats. It is concluded that although the cardiovascular response of fawn-hooded rats to 5-HT challenge is very different from that of Wistar rats, this difference is not reflected in marked alterations in 5-HT-induced intestinal secretion. This is consistent with 5-HT stimulating secretion via the activation of several different receptor subtypes so that any changes in the receptor profile in fawn-hooded rats results in little alteration in the overall intestinal response.