Noradrenaline inhibits exocytosis via the G protein βγ subunit and refilling of the readily releasable granule pool via the α(i1/2) subunit.

The Journal of Physiology
Ying ZhaoGeoffrey W G Sharp

Abstract

The molecular mechanisms responsible for the 'distal' effect by which noradrenaline (NA) blocks exocytosis in the β-cell were examined by whole-cell and cell-attached patch clamp capacitance measurements in INS 832/13 β-cells. NA inhibited Ca(2+)-evoked exocytosis by reducing the number of exocytotic events, without modifying vesicle size. Fusion pore properties also were unaffected. NA-induced inhibition of exocytosis was abolished by a high level of Ca(2+) influx, by intracellular application of antibodies against the G protein subunit Gβ and was mimicked by the myristoylated βγ-binding/activating peptide mSIRK. NA-induced inhibition was also abolished by treatment with BoNT/A, which cleaves the C-terminal nine amino acids of SNAP-25, and also by a SNAP-25 C-terminal-blocking peptide containing the BoNT/A cleavage site. These data indicate that inhibition of exocytosis by NA is downstream of increased [Ca(2+)](i) and is mediated by an interaction between Gβγ and the C-terminus of SNAP-25, as is the case for inhibition of neurotransmitter release. Remarkably, in the course of this work, a novel effect of NA was discovered. NA induced a marked retardation of the rate of refilling of the readily releasable pool (RRP) of secretor...Continue Reading

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Citations

Mar 1, 2012·ACS Chemical Neuroscience·Christopher A WellsHeidi E Hamm
Jan 12, 2011·Proceedings of the National Academy of Sciences of the United States of America·Ying WangMeisheng Jiang
Feb 7, 2012·Proceedings of the National Academy of Sciences of the United States of America·Guanghua TangMeisheng Jiang
Apr 12, 2012·American Journal of Physiology. Cell Physiology·Susanne G Straub, Geoffrey W G Sharp
Dec 6, 2012·American Journal of Physiology. Endocrinology and Metabolism·Tara A SchwetzDavid W Piston
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Apr 5, 2013·PloS One·Jennie Garcia-OlivaresGonzalo E Torres
Jun 21, 2014·Experimental & Molecular Medicine·Michelle E KimplePatrick J Casey
Jan 18, 2014·Blood·Brant E Isakson
Apr 14, 2016·The Journal of Endocrinology·Ying ZhaoGeoffrey W G Sharp
Oct 25, 2013·Molecular Biology of the Cell·Ali PedramEllis R Levin
Feb 3, 2019·The Journal of Biological Chemistry·Zack ZurawskiHeidi E Hamm
May 21, 2014·Journal of Diabetes Investigation·Mitsuhisa KomatsuYoshihiko Sato
Jul 21, 2010·The Journal of Physiology·Ying ZhaoGeoffrey W G Sharp
Nov 13, 2020·Frontiers in Cell and Developmental Biology·Michael A KalwatMelanie H Cobb
Jan 24, 2018·Molecular and Cellular Endocrinology·Amy C KellySean W Limesand

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