Vasodilatation elicited by 5-HT1A receptor agonists in constant-pressure-perfused rat kidney is mediated by blockade of alpha 1A-adrenoceptors
| Autor: | Rainer Boer, Norbert Kolassa, Manfrid Eltze, Karl Sanders |
|---|---|
| Rok vydání: | 1991 |
| Předmět: |
Male
medicine.medical_specialty Kidney Cortex Adrenergic receptor Swine Urapidil In Vitro Techniques Dinoprost Potassium Chloride Renal Circulation Norepinephrine Radioligand Assay Vas Deferens Internal medicine Flesinoxan medicine Radioligand Animals 5-HT receptor Adrenergic alpha-Antagonists Pharmacology Membranes Chemistry Ipsapirone Muscle Smooth Rats Inbred Strains Receptors Adrenergic alpha Rats Perfusion Vasodilation Endocrinology Mechanism of action Barium Receptors Serotonin 5-HT1A receptor Serotonin Antagonists medicine.symptom medicine.drug |
| Zdroj: | European journal of pharmacology. 202(1) |
| ISSN: | 0014-2999 |
| Popis: | The vasodilator mechanism of the putative serotonin 1A (5-HT) receptor agonists, urapidil, 5-methyl-urapidil, ipsapirone. flesinoxan and 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) was investigated in constant-pressure perfused rat kidneys. The compounds (10 −2 −10 −7 mol bolus injection) neither enhanced basal flow nor evoked vasodilatation in kidneys preconstricted by 27 mM KCl, 1.5 mM BaCl 2 or 10 −6 M prostaglandin (PG)F 2α , but evoked a dose-dependent, reversible and spiroxatrine-resistant increase in vasodilatation of organs preconstricted by 6 × 10 −7 M nomadrenaline. 5-Carboxamidotryptamine and sumatriptan did not reverse the vasoconstriction induced by all stimuli or that induced by noradrenaline in the presence of 5-HT 2 plus 5-HT, receptor blockade. No correlation for the vasorelaxant drugs was found between their −log ED 50 in rat kidney and pK i values at 5-HT 1A binding sites in pig cortex as determined in radioligand experiments. The relaxation in rat kidney induced by 5-HT 1A receptor agonists and α 1A -adrenoceptor-selective antagonists (WB 4101 and (+)-niguldipine) was significantly correlated with pK i values at α 1A binding sites in rat cortex and the pA 2 : values derived from contraction studies for competitive antagonism at α 1 -adrenoceptors in prostatic portions of the rat vas deferens, but differed from pK i values for α 1B binding sites in rat cortex. Thus, the vasodilator effect of the 5-HT 1A receptor agonists urapidil, 5-mcthyl-urapidil, ipsapirone. flesinoxan and 8-OH-DPAT in the noradrenaline-perfused rat kidney appears to be mediated by their concomitant α 1A -adrenoceptor blockade. No evidence for a vasodilator effect mediated through 5-HT 1A receptors was found under our experimental conditions. |
| Databáze: | OpenAIRE |
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