Role of neuropeptide-sensitive L-type Ca2+ channels in histamine release in gastric enterochromaffin-like cells

Peptides release histamine from enterochromaffin-like (ECL) cells because o f elevation of intracellular Ca2+ concentration ([Ca2+](i)) by either recep tor-operated or voltage-dependent Ca2+ channels (VDCC). To determine whethe r 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 a-loaded cells was used to measure [Ca2+](i), and histamine was assayed by RIA. Cells were depolarized by increasing extracellular K+ concentrations or by 20 mM tetraethylammonium (TEA(+)). Cell depolarization increased tran sient and steady-state [Ca2+](i) and resulted in histamine release, depende nt on extracellular Ca2+. These K+- or TEA(+)-dependent effects on histamin e release from ECL cells were coupled to activation of parietal cells in in tact rabbit gastric glands, and L-type channel blockade by 2 mu M nifedipin e inhibited 50% of [Ca2+](i) elevation and histamine release. N-type channe l blockade by 1 mu M omega-conotoxin GVIA inhibited 25% of [Ca-i(2+]) eleva tion and 14% of histamine release. Inhibition was additive. The effects of 20 mM TEA(+) were fully inhibited by 2 mu M nifedipine. Both classes of Ca2 + channels were found in ECL cells, but not in parietal cells, by RT-PCR. N ifedipine reduced PACAP-induced (but not gastrin-stimulated) Ca2+ entry and histamine release by 40%. Somatostatin, peptide YY (PYY), and galanin dose dependently inhibited L-type Ca2+ 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 s omatostatin, PYY, and galanin by interaction with a G(i) or G(o) protein.