AJP - Gastrointestinal and Liver Physiology, Vol 248, Issue 3 360-G368, Copyright © 1985 by American Physiological Society
Tricyclic antidepressants and acid secretory response of rabbit gastric cells
S. Batzri
Tricyclic antidepressants have been tested for their effect on the
H2-receptor-mediated changes in cAMP, O2 consumption, and acid secretion in
mucosal cells isolated from rabbit stomach. Amitriptyline (AMT) inhibited
the action of histamine on both cAMP generation and O2 consumption in an
apparent competitive fashion without altering these parameters in
unstimulated cells. The onset of this inhibition was rapid and the time at
which the increases in these functions had reached steady state was not
changed. The Schild regression line for AMT was close to unity, and its Ki
values for cAMP production or O2 consumption were 0.75 microM AMT.
Imipramine and nortriptyline also caused a rightward shift in the
dose-response curve of histamine-induced cAMP generation. The inhibitory
action of AMT was specific to histamine in that AMT neither altered the
effect of isobutylmethylxanthine on cAMP and respiration nor inhibited the
increase in respiration caused by carbachol. However, at relatively high
concentrations (250-500 microM), AMT inhibited the increase in cAMP caused
by 5 and 100 microM prostaglandin E1 and inhibited the increase in
respiration caused by both dibutyryl cAMP (DBcAMP) and by the combination
of DBcAMP plus carbachol. Antidepressant drugs were also very potent
inhibitors of acid formation as measured by [14C]aminopyrine accumulation
(Ki, 1 microM). They inhibited acid formation in control cells, in cells
stimulated by histamine, carbachol, and DBcAMP, and also the potentiated
response to carbachol plus histamine or DBcAMP. The onset of this
inhibition was also rapid, and adding 5 microM AMT to the cell suspension
either together with histamine or after stimulation by histamine caused a
rapid decline in aminopyrine accumulation.(ABSTRACT TRUNCATED AT 250 WORDS)
