Adenylate cyclase uncoupled beta-adrenergic receptors in salamander proximal tubules.
The isolated perfused proximal tubule of the neotenic salamander Ambystoma tigrinum responds with either a hyperpolarization or depolarization of both the basolateral cell membrane and transepithelial potentials following the addition of 10(-5) M isoproterenol to the bath superfusate. Both responses were blocked by 10(-6) M propranolol but neither response was mimicked by 10(-4) M cAMP. beta-Adrenergic binding studies of individual microdissected proximal tubules using (-)-[3H]CGP-12177 as a hydrophyllic radioligand and (+/-)-timolol (0.1 mM) as the displacer drug revealed two distinct populations of proximal tubules possessing either low (KD = 153.8 nM; Bmax = 110.2 fM/mm) or high affinity (KD = 12.0 nM: Bmax = 3.9 fM/mm) binding characteristics. Competition studies indicated that the bound (-)-[3H]CGP-12177 behaved as a typical beta-adrenergic ligand, being displaced by (-)-isoproterenol but not by (+)-isoproterenol or (-)-phenylephrine. However, neither appeared to be coupled to the adenylate cyclase system. These data suggest the presence of functional beta-adrenergic receptors that do not appear to be coupled to the adenylate cyclase system.
Morgunov
N S
NS
Department of Physiology and Biophysics, Dalhousie University, Halifax, NS, Canada.
Hirsch
D J
DJ
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000557:Ambystoma; D000818:Animals; D000242:Cyclic AMP / Q000494:pharmacology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D007700:Kinetics; D010477:Perfusion; D010656:Phenylephrine / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D011869:Radioligand Assay; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*
D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D010656:Phenylephrine; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D007545:Isoproterenol; C033394:CGP 12177