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

• Published in: British journal of pharmacology 1992-10, Vol.107 (2), p.322-328
• Main Authors: Tadipatri, Sreekanth, Feniuk, Wasyl, Saxena, Pramod R.
• Format: Article
• Language: English
• Subjects: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; 2‐methyl‐5‐hydroxytryptamine; 5‐HT receptors; 5‐hydroxytryptamine; Animals; Biological and medical sciences; Blood vessels and receptors; Fundamental and applied biological sciences. Psychology; In Vitro Techniques; Indoles - pharmacology; Muscle Contraction - drug effects; Muscle, Smooth, Vascular - drug effects; Prostaglandin Endoperoxides, Synthetic - pharmacology; rabbit renal artery; Rabbits; Receptors, Serotonin - physiology; Renal Artery - drug effects; Renal Artery - physiology; Serotonin - analogs & derivatives; Serotonin - pharmacology; Serotonin Antagonists - pharmacology; Serotonin Receptor Agonists - pharmacology; Tropanes - pharmacology; Tropisetron; Vasoconstriction - drug effects; Vertebrates: cardiovascular system; α‐methyl‐5‐hydroxytryptamine
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.1992.tb12745.x

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.