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Vol. 61, Issue 1, 65-72, January 2002

Allosteric Modulation of beta 2-Adrenergic Receptor by Zn2+

Gayathri Swaminath, Jacqueline Steenhuis, Brian Kobilka, and Tae Weon Lee

Howard Hughes Medical Institute, Stanford University Medical School, Stanford, California

Zn2+ is abundant in the brain, where it plays a role in the function of a number of enzymes, structural proteins, and transcription factors. Zn2+ 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, Zn2+ may play a physiological role in regulating the function of postsynaptic channels and receptors. We characterized the effect of Zn2+ on the functional properties of the beta 2-adrenergic receptor (beta 2AR). We found that physiological concentrations of Zn2+ increased agonist affinity and enhanced cAMP accumulation stimulated by submaximal concentrations of the beta AR agonist isoproterenol. These results provide evidence that Zn2+ released at nerve terminals may modulate signals generated by the beta 2AR in vivo.

Copyright © 2002 by The American Society for Pharmacology and Experimental Therapeutics


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Copyright © 2002 by the American Society for Pharmacology and Experimental Therapeutics