title: Phasic contractions of the rat portal vein depend on intracellular Ca2+ release stimulated by depolarization.
abstract: The phasic contraction to phenylephrine of the rat isolated portal vein was investigated using functional studies. Phasic contractions to phenylephrine and caffeine could be produced after several minutes in Ca(2+)-free Krebs solution, which were inhibited by cyclopiazonic acid or ryanodine. The phenylephrine and caffeine contractions were abolished, however, within 10 min in Ca(2+)-free Krebs solution and by nifedipine. This indicated the Ca(2+) stores were depleted in the absence of Ca(2+) influx through voltage-gated channels. The phasic contraction to phenylephrine was also abolished by niflumic acid even in Ca(2+)-free Krebs solution. This showed that the response depended on intracellular Ca(2+) release stimulated directly by depolarization, resulting from opening of Ca(2+)-activated Cl(-) channels, but did not require Ca(2+) influx. In support of this, K(+)-induced phasic contractions were also produced in Ca(2+)-free Krebs solution. The phenylephrine but not K(+)-induced phasic contractions in Ca(2+)-free Krebs solution were inhibited by ryanodine or cyclopiazonic acid. This would be consistent with Ca(2+) release from more superficial intracellular stores (affected most by these agents), probably by inositol 1,4,5-trisphospate, being required to stimulate the phenylephrine depolarization.
authors.affiliation: Department of Pharmacology, University College London, Gower Street, London WC1E 6BT, United Kingdom. r.burt@ucl.ac.uk
authors.forename: Richard P
authors.initials: RP
authors.lastname: Burt
mesh_terms: D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000493:pharmacokinetics*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology; D018118:Chloride Channels / Q000502:physiology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004558:Electric Stimulation; D007552:Isotonic Solutions / Q000494:pharmacology; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D009544:Niflumic Acid / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011169:Portal Vein / Q000502:physiology*; D011188:Potassium / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D018118:Chloride Channels; D016861:Cyclooxygenase Inhibitors; D007552:Isotonic Solutions; C051865:Krebs-Ringer solution; D010726:Phosphodiesterase Inhibitors; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D002110:Caffeine; D009544:Niflumic Acid; D011493:Protein Kinase C; D009543:Nifedipine; D011188:Potassium; D002118:Calcium