Selective action of two aporphines at alpha 1-adrenoceptors and potential-operated Ca2+ channels
| Autor: | S. Chuliá, Claire Lugnier, M. Pilar D'ocon, M. Dolores Ivorra |
|---|---|
| Rok vydání: | 1993 |
| Předmět: |
Male
Receptor complex Aporphines Apomorphine Stereochemistry Phosphodiesterase Inhibitors Molecular Conformation In Vitro Techniques Muscle Smooth Vascular Potassium Chloride chemistry.chemical_compound Norepinephrine Radioligand Assay medicine Prazosin Boldine Animals Aporphine Rats Wistar Evoked Potentials Pharmacology Membranes Alkaloid Dihydropyridine Phosphodiesterase Receptors Adrenergic alpha Rats Antitussive Agents Mechanism of action chemistry Cattle Calcium Channels medicine.symptom medicine.drug Muscle Contraction |
| Zdroj: | European journal of pharmacology. 231(2) |
| ISSN: | 0014-2999 |
| Popis: | Contractions evoked by noradrenaline (1 μM) or a depolarizing solution of 60 mM KCI were concentration dependently depressed by the aporphine alkaloids (S)-boldine and (R)-apomorphine in rataorta. Both drugs had a greater inhibitory potency on the contraction elicited by noradrenaline. Dose-response curves for noradrenaline were shifted to the right in presence of (S)-boldine. (R)-Apomorphine acted by a complex mechanism at α 1 -adrenoceptors and its inhibitory effects was irreversible. The conformational features of these alkaloids may explain their different behaviour at α 1 -adrenoceptors. In Ca 2+ -free solution, the alkaloids inhibited the contraction evoked by noradrenaline but did not modify (apomorphine) or increase (boldine) the contractile response induced by caffeine. Both alkaloids interacted with [ 3 H]prazosin binding and with the benzothiazepine binding site of the Ca 2+ entry receptor complex but had no effect at the dihydropyridine binding site in the rat cerebral cortex. Both drugs showed some selectivity as inhibitors of [ 3 H]prazosin binding as opposed to [ 3 H]d-cis ditiazem binding. (R)-Apomorphine slightly inhibited one of the two forms of the Ca 2+ -independent, low K m cyclic AMP-phosphodiesterase (type IV), whereas it did not have a significant effect on the other phosphodiesterase forms. (S)-Boldine had negligible inhibitory effects on all phosphodiesterase forms. The present study provides evidence that (S)-boldine and (R)-apomorphine have interesting properties as Ca 2+ entry blockers (through the benzothiazepine receptor site in the Ca 2+ channel) and at α 1 -adrenoceptors. |
| Databáze: | OpenAIRE |
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