Conventional-type protein kinase C contributes to phorbol ester-induced inhibition of rat myometrial tension.
1 Phorbol ester decreases muscle tension in the rat myometrium, and the effect is more potent in late-pregnant myometrium than in nonpregnant myometrium. In the present study, we have examined the contribution of protein kinase C (PKC) isoforms to the phorbol ester-induced inhibition of tension in rat uterine smooth muscle. 2 Thymeleatoxin (THX), a selective activator of conventional-type PKC (cPKC), and 12-deoxyphorbol 13-isobutyrate (DPB), an activator of pan PKC, inhibited the tension induced by high K(+), and inhibitions were significantly increased in pregnant myometrium compared to nonpregnant myometrium. The inhibition by DPB and THX of high K(+)-induced tension was significantly attenuated when PKC was downregulated by long-term pretreatment with THX and inhibited by Go6976, a cPKC inhibitor. 3 Of the cPKCs, PKC alpha is predominantly expressed in the rat myometrium, as detected by Western blot analysis. The expression of PKC alpha gradually increases from the beginning of gestation, reaching a maximum at day 21 of pregnancy. Treatment with DPB induced PKC alpha to translocate from the cytosol to the membrane in the pregnant myometrium. PKC epsilon and PKC zeta, other dominant PKC isoforms in the rat myometrium, decrease during gestation, reaching a minimum in late pregnancy. 4 These results suggest that cPKC may be at least partly involved in the PKC-mediated inhibition of muscle tension in the rat myometrium.
Kim
Bokyung
B
Department of Physiology, College of Medicine, Konkuk University, Danwol-dong 322, Choongju 380-701, Korea. bkkin2@kku.ac.kr
Kim
Yoon-Sun
YS
Ahn
Jiyun
J
Kim
Junghwan
J
Cho
SungIl
S
Won
Kyung-Jong
KJ
Ozaki
Hiroshi
H
Karaki
Hideaki
H
Lee
Sang-Mok
SM
D000818:Animals; D002227:Carbazoles / Q000494:pharmacology; D020536:Enzyme Activators / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D009215:Myometrium / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology; D010703:Phorbol Esters / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism* / Q000502:physiology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051571:Protein Kinase C-alpha; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014590:Uterine Contraction / Q000187:drug effects* / Q000378:metabolism
D002227:Carbazoles; D020536:Enzyme Activators; D007211:Indoles; D007527:Isoenzymes; D010703:Phorbol Esters; C081021:Go 6976; C039067:12-deoxyphorbol 13-isobutyrate; C080287:thymeleatoxin; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; D011188:Potassium