Beta-adrenergic receptor subtypes and subcellular compartmentation of cyclic AMP and cyclic AMP-dependent protein kinase in rabbit cardiomyocytes.
In purified ventricular myocytes from adult rabbit, beta-adrenergic stimulation causes cyclic AMP accumulation and cyclic AMP-protein kinase activation in both particulate and soluble fractions of the cell, whereas prostaglandin E1 elevates cyclic AMP and cyclic AMP-protein kinase activity in the soluble fraction exclusively. Only activation of particulate cyclic AMP-protein kinase activity results in phosphorylase b----a conversion. Using radioligand binding technics, we have determined whether beta 1- and beta 2-receptor subtypes mediate beta-adrenergic effects in particulate and soluble subcellular compartments, respectively. The non-selective antagonist [125I]iodocyanopindolol binds to intact ventricular myocytes with KD of 25 pM and a Bmax of 2.6 X 10(5) receptors/myocyte. Competition for [125I]iodocyanopindolol binding to intact myocytes by the beta-receptor subtype-specific antagonists practolol (beta 1) and zinterol (beta 2) results in monophasic curves with antagonist KD values of 1 microM and 1.5 microM, respectively. We conclude that adult rabbit cardiac myocytes do not possess detectable beta 2 receptors. Further, the ability of isoproterenol to cause elevation of cyclic AMP in two functionally distinct regions within the myocyte must pertain to the actions of a single subtype of beta-receptor, the beta 1-receptor.
D000527:Alprostadil / Q000494:pharmacology; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism*; D004983:Ethanolamines / Q000378:metabolism; D066298:In Vitro Techniques; D020120:Iodocyanopindolol; D007545:Isoproterenol / Q000494:pharmacology; D009206:Myocardium / Q000378:metabolism*; D006005:Phosphorylases / Q000378:metabolism; D010869:Pindolol / Q000031:analogs & derivatives / Q000378:metabolism; D011217:Practolol / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism*; D011817:Rabbits; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism
D004983:Ethanolamines; D011943:Receptors, Adrenergic, beta; C002904:zinterol; D020120:Iodocyanopindolol; D010869:Pindolol; D000242:Cyclic AMP; D006005:Phosphorylases; D011494:Protein Kinases; D000527:Alprostadil; D007545:Isoproterenol; D011217:Practolol