Ontogeny of hepatic insulin and glucagon receptors and adenylate cyclase in rabbit.
In rabbit liver plasma membranes (LPM), specific binding of 125I-insulin rapidly increased in late gestation and peaked at birth, declining thereafter. In contrast, 125I-glucagon binding was lowest in late gestation, somewhat higher at birth, and increased by 48 h although only to 20-25% of adult. These changes in binding were due to changing numbers of receptors involving predominantly high affinity sites for insulin and low affinity sites for glucagon, with only minor changes in affinity. Despite measurable glucagon receptors by birth, fetal LPM produced no increment above basal in cAMP production with maximal doses of glucagon (10(-6) M), prostaglandin E1 (10(-4) M), or epinephrine (10(-4) M). Near birth only NaF (10 mM) produced a modest but significant increment in cAMP. By 2 h postbirth, all stimuli evoked significant increments in cAMP production that increased progressively but was still only 15-20% of adult at 48 h. Furthermore, although specific binding of cholera toxin was greater in fetal LPM (11 +/- 1 vs. 6 +/- 1%), cholera toxin-stimulated cAMP production increased by only 12-26% above basal in the fetus compared with 220% in adult. Markers of membrane purity including 5'-nucleotidase, phosphodiesterase, and insulin or glucagon degradation were not different in fetus and adult. We conclude that receptors and components of the adenylate cyclase complex mature independently; initial coupling occurs between the G/F regulatory protein and the catalytic unit (NaF but not hormonal activation) followed within hours of birth by coupling to the hormone receptor.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000375:Aging; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000378:metabolism; D005934:Glucagon / Q000378:metabolism*; D007328:Insulin / Q000031:analogs & derivatives / Q000378:metabolism; D008099:Liver / Q000196:embryology / Q000254:growth & development* / Q000378:metabolism; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D011247:Pregnancy; D011817:Rabbits; D011972:Receptor, Insulin / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D018027:Receptors, Glucagon
D007328:Insulin; D011956:Receptors, Cell Surface; D018027:Receptors, Glucagon; C008147:insulin, iodo-; D005934:Glucagon; D011972:Receptor, Insulin; D010727:Phosphoric Diester Hydrolases; D000262:Adenylyl Cyclases