Attenuated "cross talk" between kappa-opioid receptors and beta-adrenoceptors in the heart of chronically hypoxic rats.
At 0.1-1 microM, U50488H, a kappa-opioid receptor agonist, inhibited the stimulatory effects of 1 microM isoprenaline, a beta-adrenoceptor agonist, on the electrically induced intracellular Ca2+ ([Ca2+](i)) transient and cAMP accumulation ("cross talk" between kappa-opioid receptors and beta-adrenoceptors) in the presence of 1 microM ICI118,551, a beta(2)-adrenoceptor antagonist in ventricular myocytes from both normoxic and chronically hypoxic rats. Pretreatment with 20 microg/ml cholera toxin increased the ADP-ribosylation of Gsalpha subunits and the electrically induced [Ca2+](i) transient in both normoxic and chronically hypoxic rats. The effects of cholera toxin were inhibited by 1 microM U50488H and the inhibitory effect of U50488H was attenuated in chronically hypoxic rats. Similarly, 1 microM forskolin also increased the electrically induced [Ca2+](i) transient and cAMP accumulation, which were both inhibited by U50488H, in both normoxic and chronically hypoxic rats. The inhibitory effects of 1 microM U50488H were significantly attenuated in chronically hypoxic rats. The results are novel findings, in that the "cross talk" between kappa-opioid receptors and beta-adrenoceptors is attenuated following chronic hypoxia. The attenuation may be due to decreased responses of Gs-protein and adenylyl cyclase to kappa-opioid receptor activation in addition to desensitization of the receptor itself.
Shan
Jian
J
Department of Physiology, Faculty of Medicine, The University of Hong Kong, SAR, China.
Yu
Xiao-Chun
XC
Fung
Man-Lung
ML
Wong
Tak-Ming
TM
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects; D006332:Cardiomegaly / Q000503:physiopathology; D002772:Cholera Toxin / Q000494:pharmacology; D002908:Chronic Disease; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005456:Fluorescent Dyes; D016257:Fura-2; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000378:metabolism; D006321:Heart / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D020239:Receptor Cross-Talk / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D017473:Receptors, Opioid, kappa / Q000502:physiology*
D000318:Adrenergic beta-Agonists; D005456:Fluorescent Dyes; D011943:Receptors, Adrenergic, beta; D017473:Receptors, Opioid, kappa; D005576:Colforsin; D000246:Adenosine Diphosphate Ribose; D002772:Cholera Toxin; D000242:Cyclic AMP; D019205:GTP-Binding Protein alpha Subunits, Gs; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D016257:Fura-2