Effects of phenylephrine on the contractile tension and cytosolic Ca2+ level in rat anococcygeus muscle.
A contractile property of phenylephrine (PE), alpha 1 agonist, on rat anococcygeus muscle was compared with that on rat aorta by simultaneously measuring changes in intracellular Ca2+ ([Ca2+]i) level and muscle tension. (1) PE (0.1-30 microM) and high K+ induced a sustained increases in [Ca2+]i level and muscle tension of both the muscles. (2) An application of verapamil (10 microM) and EGTA (4 mM) decreased the PE- or high K(+)-increased tension and [Ca2+]i level in both the muscle, respectively. (3) A cumulative application of PE or high K+ to anococcygeus muscle and aorta exhibited a positive relationship between [Ca2+]i and developed tension. The developed tension by PE was greater than that by high K+ at the same level of [Ca2+]i only in the aorta. A difference of regression slopes in the relationship between [Ca2+]i level and muscle tension under PE- and high K(+)-treatments in aorta was significant, but that in anococcygeus muscle was not. (4) An application of PE to anococcygeus muscle in Ca2+ free medium elicited a small transient contractile tension and increase in [Ca2+]i level, but that to aorta showed a large and transient increase in both the parameters. (5) Phorbol ester, DPB (1 microM), did not affect muscle tension or [Ca2+]i level in anococcygeus muscle, but DPB induced greater increases in aorta. (6) An application of PE (10 microM) with GTP produced a left shift in the pCa-tension curve in the beta-escin-permeabilized fiber of the anococcygeus muscle. In summary, it is suggested that the sustained contraction induced by PE in anococcygeus muscle is involved with the increases in [Ca2+]i which is due to Ca2+ influx mediated by alpha 1 receptor, but scarcely to Ca2+ release from the intracellular storage, and that an increase in Ca2+ sensitivity to PE is found only in the permeabilized anococcygeus muscle. The Ca(2+)-independent contractile mechanism in PE response as seen in aorta is probably to be absent in anococcygeus muscle. Moreover, it seems that the effect of the drug acting protein kinase C on anococcygeus muscle is extremely lesser than that on aorta.
Shimizu
K
K
Division of Veterinary Pharmacology, Nippon Veterinary and Animal Science University, Tokyo, Japan.
Kaneda
T
T
Chihara
H
H
Kaburagi
T
T
Nakajyo
S
S
Urakawa
N
N
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism; D009529:Nicardipine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014700:Verapamil / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D002121:Calcium Channel Blockers; D010656:Phenylephrine; D014700:Verapamil; D009529:Nicardipine; D002118:Calcium