title: Role of neuropeptide-sensitive L-type Ca(2+) channels in histamine release in gastric enterochromaffin-like cells.
abstract: Peptides release histamine from enterochromaffin-like (ECL) cells because of elevation of intracellular Ca(2+) concentration ([Ca(2+)](i)) by either receptor-operated or voltage-dependent Ca(2+) channels (VDCC). To determine whether VDCCs contribute to histamine release stimulated by gastrin or pituitary adenylate cyclase-activating polypeptide (PACAP), the presence of VDCCs and their possible modulation by peptides was investigated in a 48-h cultured rat gastric cell population containing 85% ECL cells. Video imaging of fura 2-loaded cells was used to measure [Ca(2+)](i), and histamine was assayed by RIA. Cells were depolarized by increasing extracellular K(+) concentrations or by 20 mM tetraethylammonium (TEA(+)). Cell depolarization increased transient and steady-state [Ca(2+)](i) and resulted in histamine release, dependent on extracellular Ca(2+). These K(+)- or TEA(+)-dependent effects on histamine release from ECL cells were coupled to activation of parietal cells in intact rabbit gastric glands, and L-type channel blockade by 2 microM nifedipine inhibited 50% of [Ca(2+)](i) elevation and histamine release. N-type channel blockade by 1 microM omega-conotoxin GVIA inhibited 25% of [Ca(2+)](i) elevation and 14% of histamine release. Inhibition was additive. The effects of 20 mM TEA(+) were fully inhibited by 2 microM nifedipine. Both classes of Ca(2+) channels were found in ECL cells, but not in parietal cells, by RT-PCR. Nifedipine reduced PACAP-induced (but not gastrin-stimulated) Ca(2+) entry and histamine release by 40%. Somatostatin, peptide YY (PYY), and galanin dose dependently inhibited L-type Ca(2+) channels via a pertussis toxin-sensitive pathway. L-type VDCCs play a role in PACAP but not gastrin stimulation of histamine release from ECL cells, and the channel opening is inhibited by somatostatin, PYY, and galanin by interaction with a G(i) or G(o) protein.
authors.affiliation: Wadsworth Veterans Affairs Hospital, Los Angeles, California 90073, USA.
authors.forename: N
authors.initials: N
authors.lastname: Zeng
authors.forename: C
authors.initials: C
authors.lastname: Athmann
authors.forename: T
authors.initials: T
authors.lastname: Kang
authors.forename: J H
authors.initials: JH
authors.lastname: Walsh
authors.forename: G
authors.initials: G
authors.lastname: Sachs
mesh_terms: D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D037361:Adenylate Cyclase Toxin; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000235:genetics* / Q000378:metabolism; D017931:DNA Primers; D004095:Dihydropyridines / Q000494:pharmacology; D019861:Enterochromaffin-like Cells / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism; D019004:Galanin / Q000494:pharmacology; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005755:Gastrins / Q000494:pharmacology; D015870:Gene Expression / Q000502:physiology; D006632:Histamine / Q000378:metabolism; D006636:Histamine Release / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009479:Neuropeptides / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000494:pharmacology; D019894:Peptide YY / Q000494:pharmacology; D037342:Pertussis Toxin; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011188:Potassium / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D011970:Receptors, Histamine H2 / Q000502:physiology; D013004:Somatostatin / Q000494:pharmacology; D013270:Stomach / Q000166:cytology; D019789:Tetraethylammonium / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D020866:omega-Conotoxin GVIA / Q000494:pharmacology
chemical_list: C495403:Adcyap1 protein, rat; D037361:Adenylate Cyclase Toxin; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D017931:DNA Primers; D004095:Dihydropyridines; D005755:Gastrins; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011970:Receptors, Histamine H2; D010566:Virulence Factors, Bordetella; D019894:Peptide YY; D013004:Somatostatin; D019789:Tetraethylammonium; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; C038806:1,4-dihydropyridine; D006632:Histamine; D019004:Galanin; D020866:omega-Conotoxin GVIA; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D011188:Potassium; D002118:Calcium