Biphasic action of phenylephrine on the Ca(2+)-activated K+ channel of human prostatic smooth muscle cells.
The elevation of cytosolic Ca2+ ([Ca2+]i) is known to regulate smooth muscle contractility. A physiological concentration of phenylephrine induced the elevation in [Ca2+]i of human prostatic smooth muscle cells; however, contraction of prostatic tissues in vitro needs a higher concentration of phenylephrine than the physiological level. To investigate this discrepancy, we investigated the functional importance of the Ca(2+)-activated K+ channel (KCa channel) of human prostatic smooth muscle cells in phenylephrine-induced contraction. Using the patch-clamp technique, the KCa channel of human prostatic smooth muscle cells was activated by phenylephrine at a physiological concentration (10(-7)-10(-5) M) but was inhibited at a higher concentration (10(-4)-10(-3) M). Phenylephrine (10(-3) M) also inhibited the KCa channel which was activated by 10 microM A23187, a calcium ionophore. Similar inhibition was obtained with 1 microM phorbol 12-myristate 13-acetate, an activator of protein kinase C (C-kinase). Both inhibitions were reversed by subsequent application of 1 nM staurosporine, a protein kinase inhibitor. These results suggested that C-kinase mediated the phenylephrine-induced inhibition of the KCa channel. In this study, a physiological concentration of phenylephrine induced activation of the KCa channel of human prostatic smooth muscle cells, which brought about membrane hyperpolarization and relaxation of human prostatic smooth muscle cells. The regulation of the KCa channel by phenylephrine may explain the need of a high concentration of phenylephrine for the contraction of prostatic tissue.
Kurokawa
Y
Y
Department of Urology, School of Medicine, University of Tokushima, Japan.
Kojima
K
K
Kagawa
S
S
Minami
K
K
Nakaya
Y
Y
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010656:Phenylephrine / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects*; D011467:Prostate / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D012680:Sensitivity and Specificity
D000316:Adrenergic alpha-Agonists; D015221:Potassium Channels; D010656:Phenylephrine; D002118:Calcium