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.
Elfellah
M S
MS
Department of Materia Medica, University of Glasgow, Stobhill General Hospital, U.K.
Reid
J L
JL
D000262:Adenylyl Cyclases / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D015536:Down-Regulation / Q000187:drug effects*; D004837:Epinephrine / Q000494:pharmacology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006352:Heart Ventricles / Q000187:drug effects; D066298:In Vitro Techniques; D020120:Iodocyanopindolol; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009132:Muscles / Q000187:drug effects / Q000502:physiology*; D009206:Myocardium / Q000201:enzymology; D010869:Pindolol / Q000031:analogs & derivatives / Q000494:pharmacology; D011869:Radioligand Assay; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D013726:Terbutaline / Q000494:pharmacology; D016276:Ventricular Function
D000318:Adrenergic beta-Agonists; D011943:Receptors, Adrenergic, beta; D020120:Iodocyanopindolol; D010869:Pindolol; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D013726:Terbutaline; D004837:Epinephrine