Inhibition of spinal protein kinase C-epsilon or -gamma isozymes does not affect halothane minimum alveolar anesthetic concentration in rats.
Anesthetic effects on receptor or ion channel phosphorylation by enzymes such as protein kinase C (PKC) have been postulated to underlie some aspects of anesthesia. In vitro studies show that anesthetic effects on several receptors are mediated by PKC. To test the importance of PKC for the immobility produced by inhaled anesthetics, we measured the effect of intrathecal injections of PKC-epsilon and -gamma inhibitors on halothane minimum alveolar anesthetic concentration (MAC) in 7-day-old and 21-day-old Sprague-Dawley rats. The inhibitors were made as solutions of 100 pmol/5 microL and were given in a volume of 5 microL (7-day-old [P7] rats) or 10 microL (21-day-old [P21] rats). Controls were saline injections or injections of the peptide carrier at the same concentration and volumes; there were six animals in each group. In P7 rats, MAC values (in percentage of an atmosphere) were 1.63 +/- 0.0727 (mean +/- SEM) in saline controls, 1.55 +/- 0.141 in carrier controls, 1.54 +/- 0.0800 in rats given PKC-epsilon, and 1.69 +/- 0.0554 in rats given PKC-gamma. In P21 animals, the values were 1.20 +/- 0.0490, 1.31 +/- 0.0124, 1.27 +/- 0.0367, and 1.15 +/- 0.0483, respectively. Injection of the inhibitors did not change MAC in either age group. These results do not support an anesthetic effect on phosphorylation as a mechanism underlying the capacity of inhaled anesthetics to prevent movement in response to noxious stimulation, and they indirectly support a direct action on receptors or ion channels.
Shumilla
Jennifer A
JA
*Department of Anesthesia, Stanford University School of Medicine, Stanford, California; and †Department of Anesthesia and Perioperative Care, University of California, San Francisco, California.
Sweitzer
Sarah M
SM
Eger
Edmond I
EI
Laster
Michael J
MJ
Kendig
Joan J
JJ
D000375:Aging / Q000378:metabolism; D018685:Anesthetics, Inhalation / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006221:Halothane / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D007278:Injections, Spinal; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D051744:Protein Kinase C-epsilon; D011650:Pulmonary Alveoli / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects / Q000201:enzymology*
D018685:Anesthetics, Inhalation; D004791:Enzyme Inhibitors; C497257:Prkce protein, rat; C087857:protein kinase C gamma; D011493:Protein Kinase C; D051744:Protein Kinase C-epsilon; D006221:Halothane