"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).
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.
Roche
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S
Laboratoire de Biochimie des Membranes, CNRS UPR-8402-INSERM U-249, Faculté de Pharmacie, Montpellier, France.
Gusdinar
T
T
Bali
J P
JP
Magous
R
R
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology*; D002766:Cholecystokinin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020109:Devazepide; D005753:Gastric Mucosa / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure*; D005755:Gastrins / Q000378:metabolism; D006636:Histamine Release / Q000187:drug effects*; D007295:Inositol Phosphates / Q000096:biosynthesis / Q000378:metabolism; D007457:Iodine Radioisotopes; D010671:Phenylurea Compounds; D011817:Rabbits; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors* / Q000145:classification / Q000378:metabolism; D013004:Somatostatin / Q000378:metabolism*
D001570:Benzodiazepinones; D005755:Gastrins; D007295:Inositol Phosphates; D007457:Iodine Radioisotopes; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin; C058121:L 365260; D013004:Somatostatin; C032740:cholecystokinin 39; C037857:gastrin heptadecapeptide, Nle(15)-; D002766:Cholecystokinin; D020109:Devazepide