Address for correspondence: Guldborg Serck-Hanssen, Department of Physiology, University of Bergen, Årstadveien 19, N-5009 Bergen, Norway. Voice: +47 55 58 63 88; fax: +47 55 58 64 10.
guldborg.serck-hanssen{at}fys.uib.no
Ann. N.Y. Acad. Sci. 971: 117-126 (2002).
The aim of the present study was to delineate possible signaling
pathways involved in acetylcholine (Ach)-induced glucose transport
in chromaffin cells, a widely applied model system for sympathetic
neurons. Acute Ach stimulation (10 min) enhanced the rate of
glucose transport through activation of both nicotinic and muscarinic
receptors. The calmodulin antagonist, W13, and the protein kinase
C (PKC) inhibitor, staurosporine, each partially depressed Ach-induced
glucose transport, with staurosporine exhibiting the stronger
inhibitory effect. Pretreating the cells with phorbol 12-myristate
13-acetate (PMA) to downregulate PKC activity did not affect
the nicotine-induced glucose transport, but completely attenuated
that activated by muscarine, suggesting that Ach activation
of transport involved both diacylglycerol-independent (PKC
)
and diacylglycerol-dependent PKCs (PKC
/PKC
). The PI 3-kinase
inhibitor, wortmannin, diminished the Ach response, consistent
with activation of the PKCs by the upstream PI 3-kinase-dependent
phosphoinositide-dependent kinase, PDK1. Cholinergic activation
strongly activated the ERK1/ERK2 cascade and p38 MAP kinase,
but only p38 MAP kinase appeared to play a role, however minor,
in nicotine-induced glucose uptake. The results are consistent
with PKCs being more important than calmodulin in coupling cholinergic
activation to glucose transport in chromaffin cells, but additional,
yet unidentified, signaling pathways appear to be needed to
obtain full activation of glucose transport in response to Ach.
Signaling
