Influence of receptor number on the cAMP response to forskolin in Chinese hamster ovary cells transfected with human beta2-adrenoceptor.
We examined the basal adenosine 3',5'-cyclic monophosphate (cAMP) levels and forskolin-induced cAMP accumulation in cultured Chinese hamster ovary cells (CHO) expressing different levels of human beta(2)-adrenoceptors. Both the basal and forskolin-induced cAMP accumulation in the cells that express higher density of beta(2)-adrenoceptors (CHO-beta(2)/H; 560 fmol/mg protein) were larger than those in the cells that express lower density of beta(2)-adrenoceptors (CHO-beta(2)/L; 270 fmol/mg protein). In addition, isoproterenol-induced cAMP accumulation was also augmented as the number of beta(2)-adrenoceptors was increased. ICI 118,551, a selective beta(2)-adrenoceptor antagonist with inverse agonist properties, decreased all the levels of cAMP observed in both cell lines. These results suggest that the agonist-independent (constitutive) activity of beta(2)-adrenoceptors plays a key role in the control of forskolin-induced cAMP accumulation.
Nakahara
Tsutomu
T
Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan nakaharat@pharm.kitasato-u.ac.jp
Maruko
Takeshi
T
Sakamoto
Kenji
K
Ishii
Kunio
K
D058672:Adrenergic beta-2 Receptor Antagonists; D000818:Animals; D016466:CHO Cells; D005576:Colforsin / Q000494:pharmacology*; D006224:Cricetinae; D003412:Cricetulus; D000242:Cyclic AMP / Q000096:biosynthesis*; D006801:Humans; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*; D014162:Transfection
D058672:Adrenergic beta-2 Receptor Antagonists; D018343:Receptors, Adrenergic, beta-2; D005576:Colforsin; D000242:Cyclic AMP