Assessment of the central and peripheral alpha_2-adrenoceptor activities by using the platelet in inflammation.

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The purpose of this study was to investigate the relationship between the platelet alpha_2-adrenoceptor activity and the central and peripheral alpha_2-adrenoceptor activities in inflammable dogs. For this purpose, the aggregatory an anti-aggregatory effects of various imidazoline or non-imidazoline alpha-adrenergic agents on canine blood platelets werer examined. Then, we examined the changes in alpha_2-adrenoceptor binding on platelet and brain membranes, and the alpha_2-adrenoceptor mediated various effects in dogs that were inflamed acutely and chronically. This study showed that imidazoline alpha-adrenergic agents and/or alpha_2-adrenoceptor blocking agents inhibit effectively the epinephrine-potentiated platelet aggregation in dogs. Therefore, it is conceivable that epinephrine-potentiated platelet aggregation in dogs is mediated by alpha_2-adrenoceptors. However, imidazoline receptors as non-adrenergic binding sites may exist on canine blood platelet. Acute inflammation induced … More by a non-lethal endotoxin injection decreased Bmax of [^3H] yohimbine binding and increased Kd in platelets, whereas in either cerebral cortex or medulla oblongata, both Bmax and Kd decreased. Pretreatment with endotoxin diminished cardiovascular effects such as bradycardia, hypotention, and increase in systemic vascular resistance induced by alpha_2-adrenoceptor agonists. Chronic arthritis induced by weekly intra-articular injection of carrageenin decreased Bmax of [^3H] yohimbine binding in platelets, and decreased Kd in either cerebral cortex or medulla oblongata. This chronic inflammation reduced the sedation, bradycardia and other effects induced by alpha_2-adrenoceptor agonists, and the effect of yohimbine in inhibiting the epinephrine-potentiatedplatelet aggregation. These results suggest that alpha_2-adrenoceptor activity is impaired in the central nervous system as well as peripheral system during acute and chronic inflammations. Therefore, platelets may in part have a significance for diagnosis of alpha_2-adrenoceptor changes in the central nervous system or peripheral system in inflamed dogs. Less