Influence of alpha- and beta-adrenoceptors on thrombin-induced serotonin release in rat platelets.
This work was designed to investigate the influence of rat platelet adrenoceptors on the early thrombin-induced serotonin release. In washed platelets prelabeled with [3H]-serotonin, adrenaline and isoproterenol both inhibited, in a dose-dependent manner, the early thrombin-induced secretion of serotonin. Inhibitory responses of both adrenaline and isoproterenol were blocked in the presence of beta-adrenoceptor antagonists, suggesting that the catecholamine acted solely through beta-adrenoceptors. However, isoproterenol inhibited the thrombin-induced serotonin release to a much greater extent than the catecholamine, suggesting that the alpha 2-component of adrenaline might account for the difference observed between the two compounds. Our observation that selective alpha 2-adrenoceptor antagonists as yohimbine and rauwolscine potentiated the inhibitory effect of adrenaline to a level close to that observed with isoproterenol, lends support to the above hypothesis. This latter result suggested that, conversely, alpha 2-adrenergic compounds might exert a counteracting effect on a full beta-adrenoceptor mediated inhibition. Although synthetic alpha 2-adrenergic agents failed to influence isoproterenol inhibitory effect, our study shows that prestimulation of beta-adrenoceptors by isoproterenol, followed by addition of adrenaline or noradrenaline markedly diminished the inhibitory effect of isoproterenol to a level close to that which characterized the inhibition observed with catecholamines, when tested alone. Our work favours the hypothesis that, in rat platelets, early after platelet stimulation, catecholamines might counteract a beta-adrenoceptor- mediated inhibition, through alpha 2-adrenoceptor sites.
Koutouzov
S
S
Cothenet-Vernoux
L
L
Marche
P
P
Dausse
J P
JP
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D004347:Drug Interactions; D004837:Epinephrine / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism*; D013917:Thrombin / Q000494:pharmacology*
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D012701:Serotonin; D013917:Thrombin; D007545:Isoproterenol; D004837:Epinephrine