Allosteric modulation of beta2-adrenergic receptor by Zn(2+).
Zn(2+) is abundant in the brain, where it plays a role in the function of a number of enzymes, structural proteins, and transcription factors. Zn(2+) is also found in synaptic vesicles and is released into synapses achieving concentrations in the range of 100 to 300 microM [Proc Natl Acad Sci USA 1997;94:13386-13387; Mol Pharmacol 1997;51:1015-1023]. Therefore, Zn(2+) may play a physiological role in regulating the function of postsynaptic channels and receptors. We characterized the effect of Zn(2+) on the functional properties of the beta2-adrenergic receptor (beta2AR). We found that physiological concentrations of Zn(2+) increased agonist affinity and enhanced cAMP accumulation stimulated by submaximal concentrations of the betaAR agonist isoproterenol. These results provide evidence that Zn(2+) released at nerve terminals may modulate signals generated by the beta2AR in vivo.
Swaminath
Gayathri
G
Howard Hughes Medical Institute, Stanford University Medical School, Stanford, California, USA.
Steenhuis
Jacqueline
J
Kobilka
Brian
B
Lee
Tae Weon
TW
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000494:Allosteric Regulation / Q000187:drug effects; D000818:Animals; D002478:Cells, Cultured; D003035:Cobalt / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004347:Drug Interactions; D006801:Humans; D007313:Insecta; D007545:Isoproterenol / Q000494:pharmacology; D009532:Nickel / Q000494:pharmacology; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D015032:Zinc / Q000494:pharmacology*
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D018343:Receptors, Adrenergic, beta-2; D003035:Cobalt; D009532:Nickel; D000242:Cyclic AMP; D015032:Zinc; D007545:Isoproterenol