Cholecystokinin-8 induces intracellular calcium signaling in cultured myenteric neurons from neonatal guinea pigs.
The responsiveness of cultured myenteric neurons to cholecystokinin (CCK-8) was examined using fura-2-based digital microfluorimetric measurement of intracellular calcium ([Ca(2+)](i)). CCK-8 (10(-10)-10(-6)M) evoked concentration-dependent increases in percentage of neurons responding (8-52%) and delta[Ca(2+)](i) (76-169 nM). Gastrin (1 microM) also induced an increase in [Ca(2+)](i) in 29+/-6% of neurons (delta[Ca(2+)](i): 71+/-3 nM). L-364,718, an antagonist for the CCK-A receptor, blocked [Ca(2+)](i) response to CCK-8. Removal of extracellular calcium eliminated CCK-induced [Ca(2+)](i) increments, as did the addition of the calcium channel inhibitors nickel (1mM) and lanthanum (5mM). Nifedipine (1-50 microM) dose-dependently attenuated CCK-caused [Ca(2+)](i) responses. CCK evokes [Ca(2+)](i) signaling in myenteric neurons by the influx of extracellular calcium, likely through L-type calcium channels.
Zhang
Weizhen
W
Department of Surgery, Michigan Gastrointestinal Peptide Center, University of Michigan, Ann Arbor, MI 48109-0331, USA.
Segura
Bradley J
BJ
Mulholland
Michael W
MW
D000818:Animals; D000831:Animals, Newborn; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects*; D002478:Cells, Cultured; D002766:Cholecystokinin / Q000494:pharmacology*; D020109:Devazepide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005755:Gastrins / Q000494:pharmacology; D006168:Guinea Pigs; D007811:Lanthanum / Q000494:pharmacology; D009197:Myenteric Plexus / Q000166:cytology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000494:pharmacology; D009532:Nickel / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology*; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*
D002121:Calcium Channel Blockers; D005755:Gastrins; D018377:Neurotransmitter Agents; D010446:Peptide Fragments; D011949:Receptors, Cholecystokinin; C410885:cholecystokinin 8; D007811:Lanthanum; D009532:Nickel; D002766:Cholecystokinin; D009543:Nifedipine; D020109:Devazepide