Jpn. J. Pharmacol. 74 (2), 155-163 (1997)
Muscarinic Autoinhibition and Modulatory Role of Protein Kinase C in
Acetylcholine Release from the Myenteric Plexus of Guinea Pig Ileum
Noriko Saitoh (1), Ritsuko Fujimoto (1), Toshiaki Ishii (1,2), Hideaki Nishio
(1), Tadayoshi Takeuchi (1,2) and Fumiaki Hata (1,2,*)
(1) Department of Veterinary Pharmacology, College of Agriculture and
(2) Department of Molecular Physiology and Biochemistry, Research Institute
for Advanced Science and Technology, Osaka Prefecture University, Sakai
593, Japan
(*) To whom correspondence should be addressed (1).
Abstract: The modulatory role of protein kinase C on phospholipase
A2, activation of which had been suggested to result in acetylcholine release
from cholinergic neurons, was studied in longitudinal muscle preparations
with the myenteric plexus of guinea pig ileum. The relationship of muscarinic
autoinhibition to the modulation was also examined. Phorbol-12,13-dibutyrate
(PDBu), an activator of protein kinase C, dose-dependently increased spontaneous
and electrical field stimulation-induced acetylcholine releases from the
preparation. The inhibitors of protein kinase C, staurosporine and calphostin
C, inhibited the stimulatory effects of PDBu, but neither inhibitor affected
spontaneous or electrical field stimulation-induced acetylcholine release
in the absence of PDBu. On the other hand, atropine significantly increased
electrical field stimulation-induced release by blocking a muscarinic autoinhibitory
mechanism. Under the autoinhibition blocked condition, U73122, an inhibitor
of phospholipase C, and staurosporine significantly inhibited the effect
of atropine on electrical field stimulation-induced release. An inhibitor
of phospholipase A2, mepacrine, inhibited PDBu-induced acetylcholine release
and also inhibited the effect of atropine on electrical field stimulation-induced
release. An activator of phospholipase A2, melittin, and a product of the
phospholipase, arachidonic acid, increased the spontaneous and electrical
field stimulation-induced releases. These results suggest that the phospholipase
C - protein kinase C system modulates acetylcholine release from cholinergic
neurons by activating phospholipase A2 in the myenteric plexus of guinea
pig ileum, and the activation of muscarinic autoreceptor may negatively
modulate acetylcholine release at a point upstream of the system.
Keywords: Acetylcholine release, Protein kinase C, Autoinhibition, Ileal
myenteric plexus (guinea pig), Phospholipase A2
Copyright© The Japanese Pharmacological Society 1997
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