Regulation of beta-adrenoceptors in the guinea pig left ventricle and skeletal muscle following chronic agonist treatment

Pretreatment of guinea pigs with adrenaline, isoprenaline or terbutaline for 7 days significantly reduced the Bmax for the radioligand [125I]cyanopindolol (ICYP) in the gastrocnemius muscle (beta 2-adrenoceptors). Pretreatment of guinea pigs with terbutaline reduced the responsiveness of gastrocnemius muscle slices adenylate cyclase to isoprenaline (10(-4) M). In the left ventricle (predominantly beta 1-adrenoceptors) pretreatment of guinea pigs with isoprenaline or adrenaline for 7 days did not alter the Bmax for ICYP. The responsiveness of adenylate cyclase to isoprenaline (10(-4) M) in left ventricle slices was significantly reduced following isoprenaline pretreatment of the guinea pigs. Thus desensitisation of beta-adrenoceptors in left ventricle and skeletal muscle developed following chronic agonist pretreatment. Reduction of beta 2-adrenoceptors in the skeletal muscle could be responsible for the desensitisation of adenylate cyclase. In the left ventricle the receptors were resistant to agonist induced down-regulation. It is proposed that other mechanisms which are tissue- and species-specific independent of the receptor subtype can be responsible for agonist-induced desensitisation in the left ventricle of the guinea pig in vivo.