title: Effect of modulating voltage-dependent calcium channels on cholecystokinin and acetylcholine-induced contractions of the guinea pig gallbladder.
abstract: The aim of this study was to investigate the role of extracellular Ca2+ utilization in cholecystokinin (CCK) and acetylcholine-induced guinea pig gallbladder contractions by using agents that modulate influx of extracellular Ca2+ through voltage-dependent calcium channels.
  
  
  METHODS
  Guinea pig gallbladder muscle strips were studied isometrically at Lmax in vitro.
  
  
  RESULTS
  (1) Acetylcholine and CCK caused dose-dependent contractions, with EDmax of 10(-4) and 10(-6) M, respectively. (2) Preventing influx of extracellular Ca2+ by incubation in Ca(2+)-free/0.1 mM EGTA solution inhibited the acetylcholine (10(-4) M)-induced contraction by 60 +/- 3% compared to only 46 +/- 5% (P < 0.05) for CCK (10(-6) M)-induced contraction. (3) Nifedipine (3 microM) inhibited the response to acetylcholine (10(-4) M) by 54 +/- 3%, compared to only 34 +/- 3% (P < 0.01) for CCK (10(-6) M). (4) Bay K 8644 (10(-7) M) significantly increased (P < 0.05) the contractile responses to low doses of each agonist: acetylcholine (10(-6) M) by 121 +/- 44% and CCK (10(-9) M) by 94 +/- 31%, but had no effect on the contraction to the EDmax of each agonist.
  
  
  CONCLUSIONS
  These studies demonstrate: (1) acetylcholine and CCK cause guinea pig gallbladder contraction by both intracellular Ca2+ release and influx of extracellular Ca2+ through voltage-dependent calcium channels; (2) the CCK-induced contraction is more dependent on intracellular Ca2+ than is acetylcholine; and (3) acetylcholine and CCK-induced contractions can by modulated by manipulating influx of extracellular Ca2+ through voltage-dependent calcium channels.
authors.affiliation: Department of Medicine, Temple University School of Medicine, Philadelphia, PA 19140, USA.
authors.forename: H P
authors.initials: HP
authors.lastname: Parkman
authors.forename: A P
authors.initials: AP
authors.lastname: Pagano
authors.forename: M A
authors.initials: MA
authors.lastname: Ringold
authors.forename: J P
authors.initials: JP
authors.lastname: Ryan
mesh_terms: D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002118:Calcium / Q000737:chemistry / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002614:Chelating Agents / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000737:chemistry; D005110:Extracellular Space / Q000737:chemistry; D005704:Gallbladder / Q000502:physiology* / Q000601:surgery; D005765:Gastrointestinal Agents / Q000494:pharmacology*; D006168:Guinea Pigs; D018738:Hexamethonium / Q000494:pharmacology; D007537:Isometric Contraction / Q000187:drug effects* / Q000502:physiology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D009543:Nifedipine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D012844:Sincalide / Q000494:pharmacology*; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002614:Chelating Agents; D005765:Gastrointestinal Agents; D018727:Muscarinic Antagonists; D018738:Hexamethonium; D013779:Tetrodotoxin; D004533:Egtazic Acid; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D001285:Atropine; D009543:Nifedipine; D012844:Sincalide; D000109:Acetylcholine; D011188:Potassium; D002118:Calcium