Differential regulation of the expression of α1-adrenergic receptor subtype genes in brown adipose tissue

Abstract

The physiological control of the expression of the genes for the alpha1-adrenoceptor subtypes was examined in rat brown adipose tissue by analysing Northern blots of poly(A)-enriched RNA with oligonucleotide probes. In control rats, alpha1B-receptor gene expression was much lower in brown adipose tissue than in liver, but the expression of both alpha1A and alpha1D was higher than in the heart, making brown adipose tissue one of the mammalian tissues with the highest expression of these subtypes. During acute exposure to cold, alpha1B-receptor gene expression was essentially unchanged, alpha1A-receptor gene expression was increased and alpha1D-receptor gene expression was transiently decreased. Noradrenaline injection could mimic these effects of acute cold exposure, indicating that the physiologically induced up- and down-regulations were due to the interaction of noradrenaline with cells within the tissue. In chronically cold-acclimated animals, alpha1B-receptor gene expression was decreased but that of the alpha1A-receptor gene remained at a level twice that of controls. alpha1D-Receptor gene expression was also somewhat decreased. It is suggested that the enhanced expression of the alpha1A-receptor gene explains the increased alpha1-receptor density in recruited brown adipose tissue reported previously. The intricate and differential regulation of alpha1-receptor gene expression and the markedly enhanced expression of the alpha1A-receptor may imply that alpha1-receptors are important for the recruitment process or for maintenance of the recruited state in this tissue.

α1-Adrenergic Stimulation Potentiates the Thermogenic Action of β3-Adrenoreceptor-generated cAMP in Brown Fat Cells

“…Many features of these receptors have subsequently been described, including up-and down-regulation in relation to sympathetic stimulation (10,(42)(43)(44)(45) and coupling of ␣ 1 -receptor stimulation to activation of second messengers and ionic events in brown fat cells (22, 24, 27, 46 -52). However, the physiological role of the ␣ 1 -receptors has remained unclear, and reported physiological effects of selective ␣ 1 -adrenergic stimulation have been minor, especially when compared with the fact that the levels of ␣ 1 -receptor mRNA in the tissue are among the highest in the body (45).…”

Cold-Induced Changes in Gene Expression in Brown Adipose Tissue: Implications for the Activation of Thermogenesis

“…However, several reports indicate a different time course of changes in the expression of the genes in response to long-term cold exposure. 30,36,53,69,107,112) These time-course changes in the gene expression suggest that functional changes in thermogenesis occur with increased duration of cold exposure.…”

“…All three subtypes are expressed in BAT. 36) The expression of the a 1B adrenergic receptor gene is at a relatively low level as compared with that of the other subtypes, and is not significantly affected by cold stimulation.…”

“…36) Chronic cold stimulation for 4 weeks increases the expression of the a 1A adrenergic receptor alone. 36) In addition, the expression of other cell-surface receptors is known to change in response to cold and/or adrenergic stimulation.…”

“…36) Chronic cold stimulation for 4 weeks increases the expression of the a 1A adrenergic receptor alone. 36) In addition, the expression of other cell-surface receptors is known to change in response to cold and/or adrenergic stimulation. Glucagon receptors and TSH receptors are members of the G protein-coupled family of receptors, and are categorized into same class with b adrenergic receptors.…”