| First Author | Zhao Y | Year | 2010 |
| Journal | J Physiol | Volume | 588 |
| Issue | Pt 18 | Pages | 3485-98 |
| PubMed ID | 20643776 | Mgi Jnum | J:329321 |
| Mgi Id | MGI:7343843 | Doi | 10.1113/jphysiol.2010.190090 |
| Citation | Zhao Y, et al. (2010) Noradrenaline inhibits exocytosis via the G protein betagamma subunit and refilling of the readily releasable granule pool via the alpha(i1/2) subunit. J Physiol 588(Pt 18):3485-98 |
| abstractText | The molecular mechanisms responsible for the 'distal' effect by which noradrenaline (NA) blocks exocytosis in the beta-cell were examined by whole-cell and cell-attached patch clamp capacitance measurements in INS 832/13 beta-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 Gbeta and was mimicked by the myristoylated betagamma-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 Gbetagamma 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 secretory granules. This retardation was specifically abolished by a Galpha(i1/2) blocking peptide demonstrating that the effect is mediated via activation of Galpha(i1) and/or Galpha(i2). |
