Identification and characterization of platelet α2- adrenoceptors and imidazoline receptors in rats, rabbits, cats, dogs, cattle, and horses

摘要

This study aimed to pharmacologically identify and characterize α2-adrenoceptors and imidazoline (I) receptors (I1- and I2-subtype) on canine, feline, bovine, equine, murine, and leporine platelet membranes. Saturation binding studies with both 3H-yohimbine and 3H-clonidine showed that α2-adrenoceptors were expressed on canine, leporine, feline, and murine platelets but not on bovine and equine platelets. In competition studies, the rank order of affinity of 6 compounds for canine platelet α2-adrenoceptors was similar to that of potency at α2A-subtype reported in human platelets. Saturation binding studies in the presence of norepinephrine showed that canine, feline, bovine, and equine platelets had I1-receptors defined by 3H- clonidine binding, but neither murine nor leporine platelets had I 1-receptors; whereas, platelets of all species had I 2-receptors defined by 3H-idazoxan binding. In competition studies, more potent compounds displayed biphasic competition curves with 3H-clonidine. The rank orders of affinity of I1 compounds for high-affinity components of I1-receptors of canine, feline, bovine, and equine platelets and I2-receptors of all species platelets were similar to those of compounds for high-affinity components reported in human I1- and I2-receptors, respectively. Guanine nucleotides inhibited the high-affinity component of naphazoline binding to canine I1-receptors, but not to I2-receptors. Furthermore, guanine nucleotides dose-dependently inhibited 3H- clonidine binding to I1-receptors; whereas, they did not interfere with 3H-idazoxan binding to I2-receptors, supporting the notion that Il-receptors may belong to a G protein-coupled receptor superfamily in canine platelets. Interspecific variations of platelet α2-adrenoceptor and imidazoline receptor expressions may explain different platelet responses to catecholamines and imidazoline α-adrenergic agents.