Neurohormonal regulation of histamine synthesis in isolated rabbit fundic mucosal cells.
In a population of rabbit fundic mucosal cells enriched in mucous and endocrine cells, gastrin and cholecystokinin octapeptide (CCK-8) were shown to increase dose-dependently histidine decarboxylase (HDC) activity with the same efficacy and high potencies [50% effective concentration (EC50) 0.389 +/- 0.041 and 0.275 +/- 0.011 nM, respectively], whereas pentagastrin was less potent (EC50 2.90 +/- 0.13 nM). L-365,260 and PD-135,666 inhibited gastrin- and CCK-8-stimulated HDC activity with a high potency [50% inhibitory concentration (IC50) 1.00 +/- 0.08 and 4.2 +/- 0.7 nM for gastrin-stimulated and 1.95 +/- 0.21 and 1.78 +/- 0.12 nM for CCK-8-stimulated HDC activity, respectively], whereas L-364,718 was 50 to 100 times less potent (EC50 100 +/- 2.5 and 91.2 +/- 3.1 nM, respectively on gastrin- and CCK-8-stimulated HDC activity). Carbachol also dose-dependently increased HDC activity (EC50 7.08 +/- 0.32 nM), and its effect was reversed by selective muscarinic-receptor antagonists with the following order of potency: pirenzepine (IC50 15.1 +/- 1.2 nM) > para-fluoro-hexahydro-siladifenidol (IC50 0.316 +/- 0.02 microM) > 11-2[(2-[(diethyl-amino)-methyl]-1-piperidinyl)acetyl]-5,11-dihydro-6H- pyrido[2,3-b][1,4]benzodiazepine-6-one (IC50 28.5 +/- 1.1 microM). Moreover, gastrin and carbachol were able to modify slightly but significantly both the Michaelis constant (Km) and the maximal velocity (Vmax) of HDC in the same way (18-20% reduction of the Km and 25-30% increase of the Vmax).(ABSTRACT TRUNCATED AT 250 WORDS)
Hollande
F
F
Laboratoire de Biochimie des Membranes, Institut National de la Santé et de la Recherche Médicale, Faculté de Pharmacie, Montpellier, France.
Bali
J P
JP
Magous
R
R
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D005748:Gastric Fundus / Q000166:cytology / Q000378:metabolism*; D005753:Gastric Mucosa / Q000166:cytology / Q000378:metabolism*; D005755:Gastrins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006636:Histamine Release / Q000187:drug effects*; D006640:Histidine Decarboxylase / Q000378:metabolism; D018727:Muscarinic Antagonists; D010418:Pentagastrin / Q000494:pharmacology; D011817:Rabbits; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors; D012844:Sincalide / Q000494:pharmacology*
D005755:Gastrins; D018727:Muscarinic Antagonists; D011949:Receptors, Cholecystokinin; D002217:Carbachol; D006640:Histidine Decarboxylase; D010418:Pentagastrin; D012844:Sincalide