Some different effect of PKC inhibitors on the acetylcholine, and endothelin-1-induced contractions of rat bronchial smooth muscle.
Although the role of protein kinase C (PKC) has been suggested in agonist-induced bronchial smooth muscle contractions, the PKC isoform(s) involved in the phenomenon are not yet clear now. Moreover, contractile agonists may have different signaling pathways in airway smooth muscle contraction. Therefore, the identification of PKC isoforms playing a role in rat bronchial smooth muscle was investigated. The presence of PKCalpha, beta, gamma, delta, epsilon, eta, zeta, lambda and iota isoforms was determined by immunoblot in the muscle. The effects of four PKC inhibitors, GF109203X, calphostin C, Gö6976 and rottlerin on acetylcholine and endothelin-1-induced bronchial smooth muscle contractions were then examined. The inhibitors were cumulatively administered after the acetylcholine or endothelin-1-induced contraction reached plateau. Since the acetylcholine-induced bronchial smooth muscle contraction was significantly inhibited by GF109203X (PKCs alpha, beta, gamma, delta and epsilon inhibitor) and calphostin C (conventional and novel PKCs inhibitor) but not by Gö6976 (PKCs alpha, beta and gamma inhibitor) and rottlerin (PKCs delta and theta inhibitor), novel PKCs might be involved in the acetylcholine-induced contraction. On the other hand, the bronchial smooth muscle contraction by endothelin-1 was significantly inhibited by GF109203X, calphostin C and Gö6976 but not by rottlerin. The conventional PKC might partially play important role in the endothelin-1 induced contraction. In conclusion, the present study clearly demonstrated the expression of multiple PKC isoforms in rat bronchial smooth muscle. Some different PKC isoforms might be partly involved between the acetylcholine and endothelin-1-induced bronchial smooth muscle contractions in rats.
Sakai
Hiroyasu
H
Department of Pharmacology, School of Pharmacy, Hoshi University, Tokyo, Japan. sakai@hoshi.ac.jp
Yamamoto
Maki
M
Chiba
Yoshihiko
Y
Misawa
Miwa
M
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001980:Bronchi; D019332:Endothelin-1 / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D019332:Endothelin-1; D007527:Isoenzymes; D047428:Protein Kinase Inhibitors; D011493:Protein Kinase C; D000109:Acetylcholine