Differences in the accessibility of the beta-adrenergic receptor in isolated hepatocytes from foetal and adult rats.
Beta-receptor number (measured by [3H]-CGP 12 177 binding) and beta-adrenergic response (measured by isoproterenol stimulated glucose liberation and isoproterenol stimulated adenylate cyclase activity) were compared in hepatocytes isolated from foetal (on day 22 of gestation), adult female and adult male rats. Beta-receptor numbers in crude membrane preparations of hepatocytes from adult female and adult male rats were found to be nearly equal (15.5 and 15.1 fmol/mg), but in crude membrane preparations of foetal rats beta-adrenergic receptor number was significantly higher (34.3 fmol/mg). Determination of number of beta-adrenergic surface receptors of intact hepatocytes showed relative high values in foetal rats (about 22,000/cell) and adult female rats (about 20,000/cell), but in male rats the number was less (about 6500/cell). Glucose liberation was stimulated by isoproterenol to the same extent in hepatocytes isolated from adult female and foetal rats (about 150% over basal), whereas no effect was found in hepatocytes isolated from adult male rats. Dose-response curves showed that in foetal rat hepatocytes glucose release was already increased by 10(-8) M isoproterenol, whereas in female rat hepatocytes at least 10(-6) M isoproterenol was required. Adenylate cyclase was stimulated by isoproterenol in lysates of hepatocytes from adult female rats by about 180% and from foetal rats by about 250%. No effects were observed using lysates of hepatocytes from adult male rats. We interpret the observed differences of beta-adrenergic responses between adult female and male rats as being primarily caused by different accessibility of the beta-receptor to the beta-agonist isoproterenol in intact hepatocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
Institute of Biochemistry, University Leipzig, Germany.
T
T
Hermsdorf
D
D
Dettmer
E
E
Hofmann
D000262:Adenylyl Cyclases / Q000378:metabolism; D000319:Adrenergic beta-Antagonists / Q000378:metabolism; D000375:Aging / Q000378:metabolism*; D000818:Animals; D005260:Female; D005947:Glucose / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*
D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; D000262:Adenylyl Cyclases; D005947:Glucose; D007545:Isoproterenol