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Protein kinase G‐induced activation of K ATP channels reduces contractility of human prostate tissue
Author(s) -
Haynes John M.,
Cook AnnaLouise M.
Publication year - 2005
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20355
Subject(s) - forskolin , diazoxide , zaprinast , endocrinology , medicine , glibenclamide , charybdotoxin , pinacidil , iberiotoxin , sodium nitroprusside , protein kinase a , contractility , potassium channel , chemistry , amrinone , nitric oxide , biology , kinase , biochemistry , stimulation , guanylate cyclase , insulin , inotrope , diabetes mellitus
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 α 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 µM) and PET‐cGMP (1 nM–100 µM), and also SNP (1 nM–100 µM), forskolin (10 µM), diazoxide (100 µM) and nifedipine (3 µM) inhibited phenylephrine (20 µM)‐induced contractions. The effect of APT‐cGMP (1 nM–100 µM) could be reversed by glibenclamide, but not by charybdotoxin. TURP tissue contained mRNA for PKG Iα, Iβ, 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 α 1 ‐adrenoceptor‐induced contractility in TURP tissue via the activation of K ATP channels. © 2005 Wiley‐Liss, Inc.