Augmentation of both hemolysate-induced contraction and activation of protein kinase C by submaximum activation in canine cerebral arteries in vitro.
Although phorbol esters, synthetic activators of protein kinase C (PKC), can stimulate large increases in the binding of cytosolic PKC to form membrane-bound PKC (PKCm, an indicator of PKC activation), the authors report that even small increases in PKCm induced by phorbol esters (8-12% of total PKC content) can be associated with significant PKC-mediated contractions in vitro (50-85% of maximum) in normal canine cerebral arteries. Increases in PKCm of similarly small magnitude were found in vitro when control artery segments were exposed to hemolysate, but only if the arterial smooth-muscle cells were first slightly depolarized by increased extracellular potassium to values of membrane potential similar to those observed in canine cerebral arteries during chronic cerebral vasospasm. These increases in PKCm (6-8% of total PKC content) coincided with a greatly augmented contractile response to hemolysate. These results show that the previous observation of only a small increase in PKCm (approximately 7% of total PKC content) after experimental subarachnoid hemorrhage in the canine model does not preclude a potentially important role for PKC-mediated contraction in the pathogenesis of cerebral vasospasm.
Kawamata
T
T
Neurosurgical Service, Massachusetts General Hospital, Boston 02114, USA.
Peterson
J W
JW
Bun
T
T
Zervas
N T
NT
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002536:Cerebral Arteries / Q000187:drug effects*; D002908:Chronic Disease; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology; D004285:Dogs; D019332:Endothelin-1 / Q000009:adverse effects; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000009:adverse effects; D006461:Hemolysis; D002546:Ischemic Attack, Transient / Q000139:chemically induced* / Q000201:enzymology / Q000209:etiology; D008564:Membrane Potentials / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009281:Naphthalenes / Q000009:adverse effects; D015240:Phorbol 12,13-Dibutyrate / Q000009:adverse effects; D010703:Phorbol Esters / Q000009:adverse effects*; D011188:Potassium / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000378:metabolism; D013314:Stress, Mechanical; D013345:Subarachnoid Hemorrhage / Q000150:complications / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000009:adverse effects*
D019332:Endothelin-1; D004791:Enzyme Inhibitors; D009281:Naphthalenes; D010703:Phorbol Esters; D014662:Vasoconstrictor Agents; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C; C058819:calphostin C; D011188:Potassium