Protein kinase G-induced activation of K(ATP) channels reduces contractility of human prostate tissue.
BACKGROUND
Human cultured prostatic stromal cells respond to protein kinase G (PKG) activators and the nitric oxide donor, sodium nitroprusside (SNP) by opening ATP-sensitive potassium channels (K(ATP) channels) to reduce nifedipine-sensitive phorbol ester-induced contractility.


METHODS
PKG activators, SNP, diazoxide, nifedipine, isoprenaline, forskolin, and Sp-8-Br-cAMP were used to inhibit alpha(1)-adrenoceptor-induced contractions in tissue from transurethral resections of the prostate (TURP). The selective K(ATP) and large conductance Ca(2+) activated K(+) (BK(Ca)) channel inhibitors, glibenclamide and charybdotoxin, respectively were used to inhibit responses to PKG activators. RT-PCR identified the K(ATP) channel subunits present in TURP tissue and cultured cells.


RESULTS
The PKG activators, APT-cGMP (1 nM-100 microM) and PET-cGMP (1 nM-100 microM), and also SNP (1 nM-100 microM), forskolin (10 microM), diazoxide (100 microM) and nifedipine (3 microM) inhibited phenylephrine (20 microM)-induced contractions. The effect of APT-cGMP (1 nM-100 microM) could be reversed by glibenclamide, but not by charybdotoxin. TURP tissue contained mRNA for PKG Ialpha, Ibeta, and II and the K(ATP) channel subunits Kir6.1, Kir6.2, SUR2B, and SUR1. Cultured stromal cells contained only Kir6.1 and SUR2B subunit mRNA. SUR1 mRNA was detected in one of five cultured epithelial cell lines.


CONCLUSIONS
PKG activators reduce alpha(1)-adrenoceptor-induced contractility in TURP tissue via the activation of K(ATP) channels. (c) 2005 Wiley-Liss, Inc.
Haynes
John M
JM
The Prostate Research Co-Operative, Victorian College of Pharmacy, Monash University, Victoria, Australia. John.Haynes@vcp.monash.edu.au
Cook
Anna-Louise M
AL
D000368:Aged; D018929:Cell Culture Techniques; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes; D008297:Male; D009119:Muscle Contraction / Q000502:physiology*; D015221:Potassium Channels / Q000502:physiology*; D011467:Prostate / Q000166:cytology* / Q000502:physiology* / Q000601:surgery; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000502:physiology
D007527:Isoenzymes; D015221:Potassium Channels; C117780:mitochondrial K(ATP) channel; D017869:Cyclic GMP-Dependent Protein Kinases