Sensitivity to protein kinase C inhibitors of nicardipine-insensitive component of high K+ contracture in rat and guinea-pig aorta.
1. In the rat and guinea-pig aorta, we observed that the contraction to hypertonically-added K+, unlike the isotonic K(+)-induced contraction, was only partially sensitive to nicardipine (0.1, 1 and 10 microM), an L-type Ca2+ channel blocker and occurred in Ca(2+)-free medium containing 50 microM EGTA. We have characterized this nicardipine-insensitive hypertonically-added K+ contraction. 2. The contraction induced by an equi-osmolar concentration of mannitol was similar in size to that evoked by hypertonically-added K+. 3. When the tissue was depleted of its internal Ca2+ stores with various agents such as phenylephrine (10 microM) cyclopiazonic acid (30 microM), thapsigargin (1 microM) or ryanodine (30 microM), or by incubation in Ca(2+)-free medium over 30 min, little effect was observed on the high K+ contracture in the presence of L-type Ca2+ channel blockade. 4. Phentolamine (10 microM) or indomethacin (10 microM) did not reduce the contraction induced by high K+. 5. Application of a protein kinase C inhibitor, H7 (10, 30 and 100 microM) or calphostin C (1 microM), reduced the high K+ contraction but not that caused by an equi-osmolar concentration of mannitol. 6. The data suggest that hypertonic K(+)-induced contraction differs from that caused by hypertonicity or depolarization per se and invokes membrane enzyme activation.
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Smooth Muscle Research Program, McMaster University, Hamilton, Ontario, Canada.
Loke
J C
JC
Kwan
C Y
CY
Daniel
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EE
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D006168:Guinea Pigs; D006982:Hypertonic Solutions; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D008353:Mannitol / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009281:Naphthalenes; D009529:Nicardipine / Q000494:pharmacology*; D010646:Phentolamine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011083:Polycyclic Compounds / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar
D006982:Hypertonic Solutions; D007546:Isoquinolines; D009281:Naphthalenes; D010879:Piperazines; D011083:Polycyclic Compounds; D008353:Mannitol; D011189:Potassium Chloride; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D009529:Nicardipine; D011493:Protein Kinase C; C058819:calphostin C; D002118:Calcium; D007213:Indomethacin; D010646:Phentolamine