The ability of gastrin, histamine, and carbachol to stimulate acid secretion by direct action on gastric parietal cells is well established but the role of intracellular Ca2+ concentration ([Ca2+]i) in mediating these effects is the subject of some controversy. To examine this issue further, secretagogue-mediated changes in [Ca2+]i in single isolated canine gastric parietal cells were examined by microspectrofluorometry of fura-2-loaded cells. Resting [Ca2+]i in single parietal cells was 63 +/- 6 (SE) nM. Carbachol, 10(-5) M, induced a maximum elevation in [Ca2+]i with an initial transient rise of 178 +/- 24 (SE) nM, which was maintained in the absence of extracellular Ca2+ and a sustained plateau of 112 +/- 20 (SE) nM, which was abolished by removal of extracellular Ca2+. Both effects were reversed by the muscarinic receptor antagonist atropine. Gastrin (10(-9)-10(-7) M) also induced a bimodal rise in [Ca2+]i with a maximal initial transient rise of 206 +/- 14 nM and a sustained plateau of 94 +/- 9 nM. Both components of the [Ca2+]i response to gastrin were reversed by the gastrin specific antagonist L 365260. Lower concentrations of gastrin (10(-10) M) induced repetitive transient increases (oscillations) in cytosolic Ca2+. The amplitude of the first spike was less than 50% of the transient rise in [Ca2+]i stimulated by 10(-8) M gastrin. The oscillations occurred at a rate of 0.9/min, gradually decreasing in amplitude within 15 min of secretagogue administration. Histamine (10(-4) M) led to a minimal rise in [Ca2+]i (less than 5% of control) in less than 10% of the canine parietal cells tested.(ABSTRACT TRUNCATED AT 250 WORDS)