"Gastrin" and "CCK" receptors on histamine- and somatostatin-containing cells from rabbit fundic mucosa-II. Characterization by means of selective antagonists (L-364,718 and L-365,260)

Biochem Pharmacol. 1991 Jul 25;42(4):771-6. doi: 10.1016/0006-2952(91)90035-4.

Abstract

In the preceding paper, by means of selective agonists to gastrin (HG-17) and cholecystokinin (CCK-39), we evidenced the existence of "gastrin-type" receptors that could regulate histamine release and "CCK-type" receptors that could stimulate somatostatin release in isolated rabbit fundic non-parietal cells (F1 cells). Furthermore, these receptors could induce phosphoinositide breakdown. To confirm the involvement of these receptor types in these biological and biochemical processes, we used selective antagonists, L-364,718 (3-(benzoylamino)-benzodiazepine) specific to "CCK-A-type" receptor and L-365,260 (3-(acylamino)-benzodiazepine) specific to "gastrin/CCK-B-type" receptor. Neither L-364,718 nor L-365,260 alone caused any significant stimulation of [3H]inositol phosphate ([3H]InsP) production and release of histamine or somatostatin-like immunoreactivity (SLI). Each analogue inhibited in a dose-dependent manner [125I]HG-17 or [125I]CCK-39 binding to F1 cells, [3H]InsP accumulation and histamine and SLI release stimulated by HG-17 or CCK-39. L-365,260 appeared to be 30-70 times more potent than L-364,718 in inhibiting [125I]HG-17 binding to F1 cells, as well as HG-17-induced [3H]InsP accumulation and HG-17-or CCK-39-enhanced histamine release (IC50 values: approximately 5-20 nM for L-365,260 and approximately 200-1500 nM for L-364,718). In contrast, L-364,718 was 200 to 400 times more potent than L-365,260 in inhibiting [125I]CCK-39 binding to F1 cells, CCK-39-induced [3H]-InsP accumulation and SLI release stimulated by CCK-39 or HG-17 (IC50 values: approximately 0.3-1 nM for L-364,718 and 100-200 nM for L-365,260). These results led to conclude: (i) the existence of a "gastrin-type" receptor related to histamine release: (ii) the existence of a "CCK-A-type" receptor related to somatostatin release; (iii) the existence of "gastrin type" and "CCK-A-type" receptors linked to the phosphoinositide breakdown pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzodiazepinones / pharmacology*
  • Cholecystokinin / analogs & derivatives
  • Cholecystokinin / antagonists & inhibitors*
  • Cholecystokinin / metabolism
  • Devazepide
  • Gastric Mucosa / cytology
  • Gastric Mucosa / metabolism
  • Gastric Mucosa / ultrastructure*
  • Gastrins / metabolism
  • Histamine Release / drug effects*
  • Inositol Phosphates / biosynthesis
  • Inositol Phosphates / metabolism
  • Iodine Radioisotopes
  • Phenylurea Compounds*
  • Rabbits
  • Receptors, Cholecystokinin / antagonists & inhibitors*
  • Receptors, Cholecystokinin / classification
  • Receptors, Cholecystokinin / metabolism
  • Somatostatin / metabolism*

Substances

  • Benzodiazepinones
  • Gastrins
  • Inositol Phosphates
  • Iodine Radioisotopes
  • Phenylurea Compounds
  • Receptors, Cholecystokinin
  • L 365260
  • Somatostatin
  • cholecystokinin 39
  • gastrin heptadecapeptide, Nle(15)-
  • Cholecystokinin
  • Devazepide