Histamine h2 receptor activation is linked to stimulation of
adenylate cyclase and phospholipase c via separate gtp dependent
pathways.
Wang, L., I. Gantz, and J. Delvalle.
Departments of Internal Medicine and Surgery, The University of
Michigan Medical Center, Ann Arbor, Michigan 48109
APStracts 3:0085G, 1996.
Previously we demonstrated that a single histamine H2 receptor can
couple to both the cAMP and IP3/[Ca2+]i signaling pathways in a
stimulatory manner. We undertook the present studies to further
characterize the post receptor events involved in H2 receptor dual
signaling. Histamine H2 receptor mediated signal transduction was
examined in isolated cell membranes prepared from purified canine
parietal cells and HEPA cells (rat hepatoma cell line) stably
transfected to express the canine H2 histamine receptor cDNA.
Histamine dose dependently stimulated both adenylate cyclase (AC,
EC50 = 2 x 10-7M) and phospholipase C (PLC, EC50 = 3.1 +/- 0 .5 x 10
-7M) activity in an H2 specific and GTP dependent manner. Cholera
toxin pretreatment abolished the stimulatory effect of histamine on
PLC activity in isolated membranes without altering binding of the H2
receptor antagonist tiotidine. Anti-Gs[alpha] dose dependently
inhibited histamine stimulated AC activity while leaving unaltered
the effect of this secretagogue on PLC activity. Although anti
-Gq[alpha] inhibited vasopressin stimulated PLC activity in HEPA cells
and carbachol stimulated PLC in parietal cells, this antibody did not
alter the action of histamine on PLC in the same membrane
preparations. Antibody against the amino and carboxyl terminus of the
common [beta] subunit of heterotrimeric G-proteins did not inhibit
histamine stimulated PLC activity. Our studies demonstrate for the
first time that activation of the H2 receptor leads to stimulation of
both AC and PLC via separate GTP dependent mechanisms.
Received 22 July 1995; accepted in final form 8 April 1996.
APS Manuscript Number G320-5.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 1 May 96