Effect of phorbol 12,13-dibutyrate on smooth muscle tone in rat stomach fundus.
We investigated the effects of phorbol 12,13-dibutyrate (PDBu), a typical protein kinase C (PKC) activator, on smooth muscle tone in the rat stomach fundus. In 5-hydroxytriptamine (5-HT)-precontracted stomach fundus strips, PDBu induced dose-dependent relaxation, but 4alpha-phorbol 12,13-didecanoate, a phorbol ester that does not activate PKC, did not induce relaxation. A PDBu-induced dose-dependent relaxation was also observed in strips precontracted with platelet-activating factor (PAF), carbachol, or 60 mM K+. In stomach fundus strips pretreated with PDBu, the contractile responses to 5-HT and PAF were completely blocked, but those induced by carbachol and endothelin-1 (ET-1) were only partially inhibited. In stomach fundus strips preincubated with carbachol in Ca2+-free medium, the Ca2+-induced contraction was decreased by preincubation with PDBu. In strips preincubated with 5-HT, PAF, or ET-1 in Ca2+-free medium, Ca2+-induced contractions were greatly inhibited by pretreatment with PDBu. These results suggest that in rat stomach fundus strips, PDBu-induced relaxation is mediated by activation of PKC. We speculate that a major factor mediating the relaxant action of PDBu in rat stomach fundus smooth muscle is represented by a reduction in Ca2+ influx via an inhibition of Ca2+ channels.
Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, Tokyo, Japan.
Takayuki
T
Matsumoto
Misaki
M
Nishiyama
Tsuneo
T
Kobayashi
Yutaka
Y
Kasuya
Katsuo
K
Kamata
D000818:Animals; D002122:Calcium Chloride / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000494:pharmacology; D005748:Gastric Fundus / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation; D009129:Muscle Tonus / Q000187:drug effects*; D009130:Muscle, Smooth / Q000502:physiology*; D015240:Phorbol 12,13-Dibutyrate / Q000008:administration & dosage / Q000494:pharmacology*; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000494:pharmacology
D019332:Endothelin-1; D010767:Phosphorylcholine; D012701:Serotonin; D015240:Phorbol 12,13-Dibutyrate; D002217:Carbachol; D002122:Calcium Chloride