Rabbit isolated renal artery contractions by some tryptamine derivatives, including 2‐methyl‐5‐HT, are mediated by a 5‐HT1‐like receptor

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Abstract
1 Despite the fact that 5-hydroxytryptamine (S-HT)-induced contractions of the rabbit isolated renal artery are mediated by a receptor belonging to the heterogeneous 5-HT1-like category, we observed that the so-called selective 5-HT3 receptor agonist, 2-methyl-5-HT, caused a concentration-dependent contraction of this vessel. This study was therefore undertaken to analyze the effects of 2-methyl-5-HT in the renal artery segments, either quiescent or precontracted with U46619 (10−7 m). α-Methyl-5-HT and 5-methoxytryptamine, which have high affinities for 5-HT2 and 5-HT4 receptors, respectively, were used for comparison. 2 In the precontracted vessel segments, the maximum contractile responses obtained with 2-methyl-5-HT, α-methyl-5-HT, 5-methoxytryptamine and 5-HT were similar to those in the quiescent segments. However the pD2 values were higher in the precontracted segments, making them about 4–100 fold more sensitive. 3 Neither MDL 72222 (10−6 m) nor tropisetron (3 × 10−6 m) suppressed renal artery contractions elicited by 5-HT, 2-methyl-5-HT, α-methyl-5-HT or 5-methoxytryptamine, thus ruling out the involvement of 5-HT3 as well as 5-HT4 receptors. 4 On the other hand, both methiothepin (10−8 and 10−7 m) and ketanserin (10−7 and 10−6 m) caused a rightward shift of agonist concentration-effect curves. The two antagonists had similar pA2 values against the different agonists tested on either quiescent or precontracted vessels, but ketanserin (apparent pA2: 6.6 to 7.0) was between 20–100 fold less potent than methiothepin (apparent pA2: 8.4 to 8.8). 5 The results of this functional study permit us to conclude that the contractile effects of 2-methyl-5-HT as well as α-methyl-5-HT and 5-methoxytryptamine on the rabbit isolated renal artery are mediated by a 5-HT1-like receptor. Since, in addition, the reported ligand binding affinity of 2-methyl-5-HT at 5-HT3 receptors is similar to both the ligand binding affinity and the functional pD2 at 5-HT1 sites, this compound cannot be regarded as a selective 5-HT3 receptor agonist. Similarly, α-methyl-5-HT and 5-methoxytryptamine have only a limited selectivity for 5-HT2 and 5-HT4 receptors, respectively.