Phasic contractions of the rat portal vein depend on intracellular Ca2+ release stimulated by depolarization.
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.
Burt
Richard P
RP
Department of Pharmacology, University College London, Gower Street, London WC1E 6BT, United Kingdom. r.burt@ucl.ac.uk
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
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