Halothane and octanol block ca2+ oscillations in pancreatic acini
by multiple mechanisms.
Deutsch, David E., John A. Williams, and David I. Yule.
Departments of Physiology, Pediatrics, and Internal Medicine,
University of Michigan Medical Center, Ann Arbor, MI 48109
APStracts 2:0096G, 1995.
This study has investigated halothane and octanol, reported inhibitors
of gap junctional permeability, for their effects on acinar cell
[Ca2+]i signaling. Halothane and octanol alone at maximal
concentrations induced a sustained rise in [Ca2+]i of 23 +/- 4 nM and
29 +/- 5 nM, respectively Cholecystokinin (CCK, 20 pM) induced
[Ca2+]i oscillations in single acinar cells within the acinus to a
peak of 275 +/- 17 nM rising from a basal level of 55 +/- 3 nM. These
oscillations were completely abolished by superfusion with both
halothane (4 mM) and octanol (1 mM), concentrations which blocked the
spread of Lucifer Yellow from cell-to-cell within an acinus. Lower
concentrations of octanol markedly reduced the oscillation frequency
(0.2, 0.5 mM octanol: reduction in oscillation frequency of 69 +/- 6
% and 43 +/- 6 % respectively). These agents however, over the same
concentration range, also exhibited similar inhibitory effects on
[Ca2+]i oscillations in single cells dispersed from the acinus
(reduction in oscillation frequency of 75 +/- 10% and 32 +/- 12% for
0.2 and 0.5 mM octanol respectively), suggesting additional effects
other than on gap junctions. Halothane inhibited 1,4,5-IP3 production
in response to both 1 and 10 nM CCK (31% and 40% inhibition,
respectively), possibly explaining its effects on [Ca2+]i
oscillations, while octanol showed no significant inhibition.
Octanol, unlike halothane, blocked 1,4,5-IP3-induced Ca2+ release
from permeabilized acini, an effect that was most pronounced at a
more physiologic 1,4,5-IP3 concentration. Octanol did not affect
1,4,5-IP3 binding to an 1,4,5-IP3 receptor preparation. In
conclusion, although halothane and octanol block gap junctional
permeability in pancreatic acinar cells, these agents also affect
1,4,5-IP3 production and Ca2+ mobilization in response to agonist
stimulation.
Received 28 October 1994; accepted in final form 11 May 1995
APS Manuscript Number G436-4.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 26 May 1995.