Phorbol Dibutyrate Induces Contractions in Bovine Cerebral Arteries by an Extracellular Calcium-independent Mechanism

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Abstract
The aim of the present study was to analyse the ability of phorbol 12,13-dibutyrate (PDB) to activate protein kinase C (PKC), measured by its capacity to translocate the enzyme from the cytosol to the membrane fraction, as well as to induce vasconstrictive responses in segments from branches of bovine cerebral arteries. PDB (0·1 μm) produced a marked translocation of PKC activity from the cytosolic to the membranous fraction. This drug induced concentration-dependent contractions which were slow in onset. The contraction elicited by PDB was reduced by the PKC inhibitor, staurosporine (1 and 10 Nm), but unaltered by both Ca2+-free medium containing 3 Mm EGTA and the Ca2+-channel antagonist, nifedipine (1 μm). Preincubation of segments with PDB (10 and 30 Nm) reduced the vasoconstriction elicited by 5-hydroxytryptamine (5-HT) in a concentration- and preincubation time-dependent manner. These data indicate that bovine cerebral arteries possess cytosolic and membranous PKC activities, that the vasoconstrictive responses induced by PDB were independent of extracellular Ca2+, that cytosolic C-kinase is translocated to the membrane and probably down-regulated by PDB, and that this enzyme is not involved in 5-HT responses, but is down-regulated by PDB.
Funding Information
  • D.G.I.C.Y.T. ((PB 87-0117))
  • F.I.S.S ((89/0078-2 and 90 E0959))
  • FAR ((91-0205))