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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.