Allosteric Modulation of β2-Adrenergic Receptor by Zn2+
2002
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 μM [ 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 β 2 -adrenergic receptor (β 2 AR). We found that physiological concentrations of Zn 2+ increased agonist affinity and enhanced cAMP accumulation stimulated by submaximal concentrations of the βAR agonist isoproterenol. These results provide evidence that Zn 2+ released at nerve terminals may modulate signals generated by the β 2 AR in vivo.
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