Involvement of extracellular calcium in gastric stimulation

Abstract
External Ca2+ was studied to determine whether it is required for initiation or maintenance of secretory parameters, including membrane elaboration of oxyntic cells, in frog gastric mucosa. Ca2+ was removed from in vitro mucosal preparations [by washing repeatedly in Ca2+-free Ringer solution and adding 0.1 mM ethylene glycol-bis(.beta.-aminoethylether)-N,N''-tetraacetic acid to the serosal solution] before (i.e., resting tissues) or after addition of stimulants, Electrophysiology [transepithelial potential difference (PD) and resistance], morphology (morphometric analysis of transmission electron micrographs) and transport (H+ secretion) were monitored. La3+ (1 mM) was added to the mucosal solution to help maintain resistance and PD. La3+ decreased tissue shunt conductance during Ca2+-free conditions, as evidenced by a decreased mucosal-serosal flux of 22Na+, presumably by preserving tight-junction integrity. Secretion was elicited by histamine alone or in combination with dibutyryl cAMP and isobutylmethylxanthine (a phosphodiesterase inhibitor). External Ca2+ is not required for the initiation of H+ secretion or the accompanying morphological changes when the combined stimulants are used, whereas H+ secretion and the morphological change showed some Ca2+ dependency when histamine alone was used. Thus, histamine-elicited secretion is apparently more sensitive to Ca2+ removal than that brought about by the combined stimulants. Long-term effects of Ca2+-free solutions on resistance, PD and H+ secretion can largely be explained by disruptive effects on tight junctions.