Rabbit isolated renal artery contractions by some tryptamine derivatives, including 2-methyl-5-HT, are mediated by a 5-HT1-like receptor
| Autor: | Pramod R. Saxena, Wasyl Feniuk, Sreekanth Tadipatri |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 1992 |
| Předmět: |
Agonist
medicine.medical_specialty Serotonin Ketanserin Indoles medicine.drug_class Tropisetron Biology In Vitro Techniques Muscle Smooth Vascular chemistry.chemical_compound Renal Artery medicine.artery Internal medicine medicine Animals Renal artery Receptor 5-HT receptor Pharmacology musculoskeletal system Prostaglandin Endoperoxides Synthetic Serotonin Receptor Agonists Endocrinology chemistry Vasoconstriction 15-Hydroxy-11 alpha 9 alpha-(epoxymethano)prosta-5 13-dienoic Acid Receptors Serotonin 2-Methyl-5-hydroxytryptamine Rabbits Serotonin Antagonists medicine.symptom medicine.drug Research Article Muscle Contraction Tropanes |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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