Functional evaluation of 5-hydroxytryptamine receptor activity in rat resistance vessels

1. To characterize 5-hydroxytryptamine (5-HT) receptors in rat perfused mesenteric vascular bed (MVB), the effect of 5-HT and related compounds was investigated by functional assay. 2. In quiescent preparations, 5-HT elicited a concentration-dependent conctractile response. After addition of ketanserin, a 5-HT2 receptor antagonist, EC50 values were significantly higher than in controls. 3. In noradrenaline (NA)-precontracted preparations, under continuous infusion of ketanserin, 5-HT, 5-carboxamidotryptamine (5-CT) and sumatriptan produced relaxation. Their rank order of relaxant potency and maximum effect were sumatriptan > 5-HT > 5-CT. Methysergide (1 microM) and spiperone (20-100 nM) caused a rightward shift of the relaxation curve to sumatriptan. These data suggest that vasodilatation in rat MVB is mediated by an 'atypical' subtype of 5-HT1-like receptor, which reveals a pharmacological profile similar to that of the 5-HT1D receptor. The involvement of both 5-HT3 and 5-HT4 receptors can be ruled out, since tropisetron (up to 10 microM) was not able to antagonize the relaxant effect by sumatriptan. 4. Under granisetron infusion (3 microM), the contractile response evoked by perivascular nervous stimulation, but not exogenous NA contraction, was significantly reduced (P < 0.001). These data demonstrate the presence of 5-HT3 receptors in peripheral neurones, modulating neurotransmitters release.