Independent regulation of beta-adrenergic receptor and nucleotide binding proteins of adenylate cyclase. Developmental and denervation-dependent responses in rat parotid.
Rat parotid gland secretion cannot be activated through beta-adrenergic stimulation of adenylate cyclase until after 2 weeks postnatal. We have studied the relationship of the levels of putative guanine nucleotide-binding regulatory components (G/F) of the cyclase system to the onset of hormone responsiveness. The effect of sympathetic denervation on the components of this system during development of secretory function also has been examined. Nucleotide-dependent, hormone-stimulated, and fluoride-stimulated adenylate cyclase activities in parotid membranes are present at low levels at birth and increase 2-fold between 14 and 18 days postnatal while beta-adrenergic receptor levels remain constant. G/F proteins, regulatory for adenylate cyclase activation, were quantitated by ADP-ribosylation in the presence of cholera toxin. Labeling of two cholera toxin-specific substrates occurs at low levels in neonatal rats and increases sharply at the critical 14-18-day period. This provides a plausible explanation for the increase in adenylate cyclase sensitivity at this time, although increases in cyclase catalytic units and/or coupling efficiency of receptor and cyclase may also be involved. In previous studies we found that animals chemically sympathectomized with 6-hydroxydopamine at birth developed elevated levels of membrane-bound beta-adrenergic receptors. The functional consequence is that treated animals show a shift (1.7-fold) toward increased sensitivity in the dose-response curve for adenylate cyclase activation by isoproterenol. However, the levels of maximal hormone- and fluoride-stimulated adenylate cyclase activities do not change, suggesting that some component distal to the receptor is limiting under both control and treated conditions, or that there are deficiencies in coupling of the receptor pool.
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002772:Cholera Toxin / Q000494:pharmacology; D002373:Cyclic AMP Receptor Protein; D006892:Hydroxydopamines / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D016627:Oxidopamine; D010306:Parotid Gland / Q000187:drug effects / Q000254:growth & development* / Q000294:innervation; D051381:Rats; D011941:Receptors, Adrenergic / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*
D002352:Carrier Proteins; D002373:Cyclic AMP Receptor Protein; D006892:Hydroxydopamines; D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D000246:Adenosine Diphosphate Ribose; D016627:Oxidopamine; D002772:Cholera Toxin; D000262:Adenylyl Cyclases; D007545:Isoproterenol