Up-regulation of beta 1-adrenoceptor messenger ribonucleic acid in the rat pineal gland: nocturnally, through a beta-adrenoceptor-linked mechanism, and in vitro, through a novel posttranscriptional mechanism activated by specific protein synthesis inhibitors.
The uniquely high concentration of beta 1-adrenoceptor mRNA (beta 1-mRNA) in the pineal gland provides a model for the regulation of GTP-binding protein (G-protein)-linked receptor gene expression within a functioning endocrine gland. By Northern analysis it has been shown that a nocturnal up-regulation of beta 1-mRNA in the rat pineal results in a 2.6-fold increase in mRNA levels at the middark phase (2400 h) compared with those at the midlight phase (1200 h). This increase is blocked by administration of the beta-adrenoceptor antagonist propranolol before the onset of darkness. In vitro studies of beta 1-mRNA expression in organ-cultured pineals has confirmed beta-adrenoceptor-linked up-regulation of beta 1-mRNA. Treatment of cultured pineals with the second messenger drugs forskolin and phorbol 12,13-dibutyrate produced mRNA responses that were again consistent with a primary role of beta-adrenoceptors in the up-regulation of beta 1-mRNA. Nuclear run-on analysis showed that the acute up-regulation of mRNA was mediated largely through a transcriptional mechanism. An additional novel mode of regulation of beta 1-mRNA was also identified; the protein synthesis inhibitors anisomycin and cycloheximide, but not puromycin and emetine, elicited an acute increase in beta 1-mRNA in cultured pineals that was not transcriptionally mediated. The mechanism underlying this mode of regulation is discussed with relation to control of the cellular immediate early gene c-fos. The facility to examine both physiological and in vitro changes in beta 1-mRNA expression in the pineal will provide further insight into the complexity that is apparent for the molecular regulation of G-protein-coupled receptors.
Carter
D A
DA
Neuropeptide Laboratory, National University of Singapore.
D000818:Animals; D000841:Anisomycin / Q000494:pharmacology; D001483:Base Sequence; D015152:Blotting, Northern; D002940:Circadian Rhythm; D005576:Colforsin / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology; D005786:Gene Expression Regulation; D008297:Male; D008969:Molecular Sequence Data; D009924:Organ Culture Techniques; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010870:Pineal Gland / Q000378:metabolism*; D011433:Propranolol / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000235:genetics* / Q000502:physiology; D014158:Transcription, Genetic
D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; D005576:Colforsin; D015240:Phorbol 12,13-Dibutyrate; D000841:Anisomycin; D003513:Cycloheximide; D011433:Propranolol; D019204:GTP-Binding Proteins