Rapid and reversible desensitisation of vascular and platelet alpha 2 adrenoceptors.
The effects of intravenous infusion with the alpha2 adrenoceptor selective agonist alpha methylnoradrenaline on pressor responses to alpha adrenoceptor agonists, alpha2 adrenoceptor mediated platelet aggregation and adenylate cyclase were examined in conscious rabbits. Pressor responses to alpha methylnoradrenaline but not phenylephrine were decreased in a dose dependent manner during methylnoradrenaline infusion at all times examined. Recovery of these responses after stopping infusion was dependent on both the dose infused and the duration of the infusion. Alpha methylnoradrenaline infusion resulted in a dose and time dependent decrease in the pro-aggregatory response of platelet to adrenaline without any significant change in the response to ADP or in the number of [3H]yohimbine binding sites. The ability of PGE1 to stimulate adenylate cyclase was not influenced by alpha methylnoradrenaline infusions. However, reversal of this stimulation by adrenaline was decreased by relatively long (30 min) infusions of the highest dose of alpha methylnoradrenaline examined. It is concluded that alpha methylnoradrenaline infusions resulted in desensitisation of all the alpha2 adrenoceptor mediated responses examined. However the time course for the desensitisation apparently differed according to the response examined.
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001792:Blood Platelets / Q000201:enzymology / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D004837:Epinephrine / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D008771:Nordefrin / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D011817:Rabbits; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D013997:Time Factors; D015016:Yohimbine / Q000097:blood
D000316:Adrenergic alpha-Agonists; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D000242:Cyclic AMP; D008771:Nordefrin; D004837:Epinephrine