Beta-adrenergic receptor coupled adenylate cyclase in rat kidney. Differential coupling in glomeruli and tubules.
[125I]Iodocyanopindolol ([125I]ICYP) was used to identify and characterize the beta-adrenoceptors in isolated rat kidney glomeruli and cortical tubules. In both the tissues, specific binding of [125I]ICYP was saturable with time and ligand concentration and showed appropriate stereospecificity and agonist rank order potency characteristic of binding to beta-adrenoceptors. Scatchard analysis revealed that the beta-adrenoceptor concentration in the glomeruli (111.1 +/- 8.9 fmol/mg protein) was about three times that in the tubules (40.1 +/- 1.8 fmol/mg protein). The dissociation constants (KD) were similar in the two tissues. Both beta 1- and beta 2-adrenoceptor subtypes were present in the glomeruli and tubules, but the beta 1-subtype was predominant, constituting greater than 80% of the total beta-adrenoceptors in the two tissues. Isoproterenol was twice as potent in competing for [125I]ICYP binding in the tubules as in the glomeruli (P less than 0.05). The slope factor (pseudo-Hill coefficient) for the isoproterenol competition curve was 0.74 +/- 0.04 in the glomeruli and 0.54 +/- 0.02 in the tubules (P less than 0.05). The nonmetabolized guanyl nucleotide analogue Gpp(NH)p caused a steepening and a 3-fold shift of the isoproterenol competition curve in both tissues. Isoproterenol-stimulated cAMP accumulation in the glomeruli was only 31% of the value in the tubules. The concentration of isoproterenol producing half-maximal stimulation (EC50) was 114 +/- 13 nM in the glomeruli and 19 +/- 3 nM in the tubules (P less than 0.05). Gpp(NH)p and forskolin caused a similar increase in cAMP accumulation over basal value in the glomeruli as in the tubules. Overall, our results indicate a decreased efficiency in the interaction between the beta-adrenergic agonist hormone, the receptor and the guanine nucleotide regulatory protein in the glomeruli as compared to the tubules.
Sundaresan
P R
PR
Department of Pharmacology, University of Rochester Medical Center, NY 14642.
Kelvie
S L
SL
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D015784:Betaxolol; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D020120:Iodocyanopindolol; D007678:Kidney Glomerulus / Q000187:drug effects / Q000201:enzymology*; D007684:Kidney Tubules / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D010869:Pindolol / Q000031:analogs & derivatives / Q000378:metabolism; D011412:Propanolamines / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D013237:Stereoisomerism
D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D005576:Colforsin; D006165:Guanylyl Imidodiphosphate; D020120:Iodocyanopindolol; D010869:Pindolol; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D015784:Betaxolol