Regulation of [Ca2+]i by secretagogue stimulation of canine gastric parietal cells

Abstract

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)

Alkaline secretion by frog gastric glands measured with pH microelectrodes in the gland lumen

“…This pointed to an electrogenic model of HCOצ secretion such as that elicited by opening of an apical anion conductance. This anion conductance, which seems to transfer Cl¦ as well as notable amounts of HCOצ (the change of alkaline secretion rate corresponded to approximately one-third of the concomitant change in short circuit current), may be activated by a rise in intracellular Ca¥ concentration such as observed after cholinergic stimulation in parietal cells (Chew et al 1992 ;Delvalle et al 1992). Since our observations with pentagastrin resemble very closely those with cholinergic stimulation, we may conclude that pentagastrin also raised intracellular Ca¥ and activated the same apical anion conductance.…”

The peripheral cholecystokinin receptors

“…Accumulation of inositol 1,4,5-trisphosphate shows biphasic kinetics, with a rapid increase involving a pertussis-toxin-insensitive pathway independent of extracellular Ca2+ and a sustained rise involving a pertussis-toxin-sensitive pathway dependent on extracellular Ca' + [268]. Changes in [Caz+], induced by gastrin stimulation were analyzed on single canine parietal cells [269]. At low gastrin concentrations causing inositol phospholipid breakdown, [Ca'+], oscillations, independent of extracellular Ca" , are detected.…”

“…At low gastrin concentrations causing inositol phospholipid breakdown, [Ca'+], oscillations, independent of extracellular Ca" , are detected. At higher gastrin concentrations, a biphasic rise with an initial transient peak followed by a sustained plateau, is observed [269] [278]. CCK is also believed to regulate contraction and/or relaxation of sphincters including the lower oesophageal sphincter [279], the pylorus [280, …”

Interactions between oxoglutarate oxidation and acid secretion in isolated rabbit gastric glands

“…First, the addition of carbachol, a gastric secretagogue that acts through an increase in [Ca2t]0 (Negulescu & Machen, 1988;Delvalle et al 1992), stimulated the rate of oxoglutarate oxidation (Table 4). This effect was only observed with non-saturating concentrations of oxoglutarate, which is in accordance with the known fact that calcium activates OGDH by lowering the apparent Km for oxoglutarate without altering the Vmax (Denton & McCormack, 1986McCormack, Halestrap & Denton, 1990 (Subero et al 1989) and isolated gastric glands (Hernandez & Chacin, 1994) that showed that carbohydrate oxidation is dependent on calcium concentration.…”

“…Stimulation by these secretagogues is accompanied by an increase in cytosolic calcium concentration ([Ca2+]e) (Negulescu & Machen, 1988;Delvalle et al 1992). Some recent findings have led to the hypothesis that the increases in [Ca2+]0 could be relayed into the mitochondria, resulting in the activation of several key dehydrogenases, and probably other steps, within the process of oxidative phosphorylation (Hernandez & Chacin, 1994).…”