Effects of guanine nucleotides and cations on agonist affinity of alpha 1-adrenoceptors in brown adipose tissue.
In order to investigate the coupling mechanism of alpha 1-adrenoceptors in brown adipose tissue, the effects of guanine nucleotides and cations on agonist binding were studied with a membrane fraction obtained from hamsters. The affinity of the alpha 1-receptor for the adrenergic agent was followed in competition experiments with [3H]prazosin. It was found that the addition of GTP diminished the affinity of the alpha 1-receptor for norepinephrine but not for the alpha-antagonist phentolamine. This effect seemed to be dependent upon the presence of Mg2+ and could not be observed in isolated cells, indicating an intracellular site of action. A reduction of the Mg2+ concentration from the conventional 10 mM to the more physiological level of 1 mM markedly increased the affinity of the receptor for norepinephrine; this effect again was agonist-specific. The addition of Na+ (150 mM) decreased the agonist affinity of the receptor. It is suggested that the (not adenylate cyclase-coupled) alpha 1-adrenergic pathway in brown adipose tissue also is regulated by guanine nucleotides and modulated by the cations Mg2+ and Na+, indicating an involvement of a guanine nucleotide binding protein. Such a system may therefore be a general mechanism for the transduction of hormone stimulation over the cell membrane.
Mohell
N
N
Nedergaard
J
J
D002001:Adipose Tissue, Brown / Q000378:metabolism*; D000316:Adrenergic alpha-Agonists / Q000378:metabolism*; D000818:Animals; D002021:Buffers; D002412:Cations / Q000494:pharmacology; D006224:Cricetinae; D006150:Guanine Nucleotides / Q000494:pharmacology*; D006160:Guanosine Triphosphate / Q000494:pharmacology; D066298:In Vitro Techniques; D008274:Magnesium / Q000494:pharmacology; D008566:Membranes / Q000378:metabolism; D008647:Mesocricetus; D011224:Prazosin / Q000378:metabolism; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D012964:Sodium / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D002021:Buffers; D002412:Cations; D006150:Guanine Nucleotides; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D006160:Guanosine Triphosphate; D012964:Sodium; D008274:Magnesium; D011224:Prazosin