An unusual Ca(2+) entry pathway activated by protein kinase C in dog splenic artery.
The characteristics of the Ca(2+) entry pathways that are activated by protein kinase C (PKC) in canine splenic artery were investigated. Phorbol 12, 13-dibutyrate (PDB) contracted tissues and increased Ca(2+) influx. PDB-induced contraction was reduced by preincubation of tissues in Ca(2+)-free Krebs' solution (1 mM EGTA) but was unaffected when Ca(2+)-free solution was applied after contraction was initiated with PDB. In contrast, (45)Ca influx and contraction induced by PDB were resistant to nifedipine, Cd(2+), Gd(3+), La(3+), or Ni(2+) whether added before or during exposure to PDB. Indeed, Cd(2+) reduced (45)Ca(2+) efflux and potentiated Ca(2+) influx, but not PDB-induced contraction. Norepinephrine (NE)-induced contractions were inhibited by preincubation in Ca(2+)-free Krebs' solution (1 mM EGTA). Nifedipine (10 microM) led to a small reduction in the NE-induced contraction but was without effect on (45)Ca(2+) influx. Pretreatment for 16 min with Cd(2+), Gd(3+), or La(3+) (each 1 mM) reduced or abolished NE-induced contraction and Ca(2+) influx. Application of these cations after exposure to NE did not affect (45)Ca(2+) influx but reduced tension. The Q(10) for the increase in (45)Ca(2+) influx was approximately 2 for high K(+) and NE, but 4 for PDB. The results suggest that stimulation of PKC in dog splenic artery activates a Ca(2+) entry pathway that is resistant to di- and trivalent cations. The inhibition of Ca(2+) influx by preincubating with cations during short-term exposure to NE may represent an action on Ca(2+) turnover that precedes activation of PKC.
Khoyi
M A
MA
Departments of Pharmacology, Physiology and Cell Biology, University of Nevada, School of Medicine, Reno, Nevada 89557-0001, USA.
Gregory
L G
LG
Smith
A D
AD
Keef
K D
KD
Westfall
D P
DP
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002412:Cations / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004533:Egtazic Acid / Q000737:chemistry; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010477:Perfusion; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology*; D013157:Splenic Artery / Q000187:drug effects; D013997:Time Factors
D002412:Cations; D015240:Phorbol 12,13-Dibutyrate; D004533:Egtazic Acid; D011493:Protein Kinase C; D009543:Nifedipine; D002118:Calcium; D009638:Norepinephrine