Ontogeny of renal beta adrenoceptors in the sheep.
The renal vasodilatory response to beta-2 adrenoceptor stimulation is greater in fetal than adult sheep. Since this phenomenon could not be explained by differences in cAMP-mediated events, we examined the ontogeny of renal beta adrenoceptor subtypes by radioligand binding using the beta adrenergic antagonist 125I-pindolol. The specific binding of 125I-pindolol was saturable, reversible, and stereoselective. Competition studies using the selective beta-1 and beta-2 adrenergic antagonists (ICI 89406 and ICI 118551, respectively) revealed two beta adrenoceptor subtypes in adult kidneys but only the beta-2 subtype in fetal kidneys. Preincubation of renal cortical membranes with either the beta-1 or the beta-2 adrenergic antagonist prior to competition studies in adult kidneys decreased specific binding and resulted in the detection of only one beta adrenoceptor subtype. Preincubation of fetal kidneys with the beta-1 adrenergic antagonist did not affect binding characteristics; preincubation of fetal kidneys with the beta-2 adrenergic antagonist markedly decreased specific binding from 64 +/- 2% (n = 4) to 29 +/- 2% (n = 3) (P less than 0.05). Analysis of Rosenthal plots revealed similar beta adrenoceptor densities and affinities between fetal and adult kidneys.(ABSTRACT TRUNCATED AT 250 WORDS)
Felder
C C
CC
Section of Pharmacology, National Institute of Mental Health, Bethesda, MD 20892.
Piccio
M M
MM
McKelvey
A M
AM
Nakamura
K T
KT
Robillard
J E
JE
Jose
P A
PA
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D000375:Aging; D000818:Animals; D001667:Binding, Competitive; D004983:Ethanolamines / Q000493:pharmacokinetics; D007545:Isoproterenol / Q000493:pharmacokinetics; D007668:Kidney / Q000098:blood supply / Q000378:metabolism*; D010869:Pindolol / Q000494:pharmacology; D011412:Propanolamines / Q000493:pharmacokinetics; D011433:Propranolol / Q000493:pharmacokinetics; D011869:Radioligand Assay; D011943:Receptors, Adrenergic, beta / Q000032:analysis / Q000187:drug effects / Q000378:metabolism*; D012756:Sheep; D014664:Vasodilation
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D004983:Ethanolamines; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; C026777:ICI 118551; C002904:zinterol; D011433:Propranolol; D010869:Pindolol; C025716:ICI 89406; D007545:Isoproterenol