Keiko Akagi (1), Ko Hasebe (2), Kazuo Watanabe (2), Taku Nagao (1) and
Tetsuro Urushidani (1,*)
(1) Laboratory of Pharmacology & Toxicology, Graduate School of Pharmaceutical
Sciences, The University of Tokyo Tokyo,113-0033, Japan
(2) Department of Drug Evaluation and Toxicological Sciences, Faculty of
Pharmaceutical Sciences, Chiba University, Chiba 263-8522,Japan
(*) To whom correspondence should be addressed.
Abstract: We examined the validity of the high K+
condition, widely used as a model to investigate the mechanism of acid secretion,
employing isolated rabbit gastric glands. When Na+ in the nutrient
solution was replaced with K+, the acid secretion monitored by
the accumulation of 14C-aminopyrine increased K+-concentration-dependently.
Stimulation of carbachol or dbcAMP was also greatly enhanced by K+.
The responses to forskolin, phorbol ester, gastrin and submaximal dose of
histamine were potentiated in the high K+ condition, but the
responses to isobutylmethylxanthine, calyculin A and the maximal dose of
histamine were not. The augmented response to carbachol was not dependent
on [Ca2+]o. Replacement of Na+ with any
other ions, including Rb+, Cs+, Li+, tetramethylammonium
and choline, increased the basal aminopyrine ratio. Most of these ions were
also effective in enhancing the response to dbcAMP, but failed to augment
the effect of carbachol. Replacement of Na+ with K+,
Rb+, Cs+ and Li+ transiently elicited acid
secretion in the isolated mouse whole stomach. These results suggest that
the high K+ is not a simple model for the direct activation of
the proton pump, but the augmentation consists of two components, i.e.,
the combined effects of low Na+ and high K+. The former
augments basal and cAMP-stimulated acid production, whereas the latter augments
acid production by any agonist except calyculin A.
Keywords: H+,K+-ATPase, Alkaline metal, Gastric
gland, Aminopyrine accumulation