Rabbit isolated renal artery contractions by some tryptamine derivatives, including 2-methyl-5-HT, are mediated by a 5-HT1-like receptor.
1. Despite the fact that 5-hydroxytryptamine (5-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). alpha-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, alpha-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 x 10(-6) M) suppressed renal artery contractions elicited by 5-HT, 2-methyl-5-HT, alpha-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 ct-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-HTI sites, this compound cannot be regarded as a selective 5-HT3 receptor agonist. Similarly, a-methyl-5-HT and 5-methoxytryptamine have only a limited selectivity for 5-HT2 and 5-HT4 receptors, respectively.
Tadipatri
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S
Department of Pharmacology, Faculty of Medicine and Health Sciences, Erasmus University Rotterdam, The Netherlands.
Feniuk
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W
Saxena
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PR
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011817:Rabbits; D011985:Receptors, Serotonin / Q000502:physiology*; D012077:Renal Artery / Q000187:drug effects* / Q000502:physiology; D012701:Serotonin / Q000031:analogs & derivatives* / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D014326:Tropanes / Q000494:pharmacology; D000077526:Tropisetron; D014661:Vasoconstriction / Q000187:drug effects*
D007211:Indoles; D011450:Prostaglandin Endoperoxides, Synthetic; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D014326:Tropanes; C042390:alpha-methylserotonin; D012701:Serotonin; D000077526:Tropisetron; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C045918:2-methyl-5-HT; C042253:bemesetron