Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.12 (PKG)
 2,515 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Potassium channels activated by membrane stretch may contribute to maintenance of relaxation of smooth muscle cells in visceral hollow organs. Previous work has identified K(+) channels in murine colon that are activated by stretch and further regulated by NO-dependent mechanisms. We have screened murine gastrointestinal, vascular, bladder, and uterine smooth muscles for the expression of TREK and TRAAK mRNA. Although TREK-1 was expressed in many of these smooth muscles, TREK-2 was expressed only in murine antrum and pulmonary artery. TRAAK was not expressed in any smooth muscle cells tested. Whole cell currents from TREK-1 expressed in mammalian COS cells were activated by stretch, and single channel recordings showed that the stretch-dependent conductance was due to 90 pS channels. Sodium nitroprusside (10(-6) or 10(-5) m) and 8-Br-cGMP (10(-4) or 10(-3) m) increased TREK-1 currents in perforated whole cell and single channel recordings. Mutation of the PKG consensus sequence at serine 351 blocked the stimulatory effects of sodium nitroprusside and 8-Br-cGMP on open probability without affecting the inhibitory effects of 8-Br-cAMP. TREK-1 encodes a component of the stretch-activated K(+) conductance in smooth muscles and may contribute to nitrergic inhibition of gastrointestinal muscles.
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PMID:TREK-1 regulation by nitric oxide and cGMP-dependent protein kinase. An essential role in smooth muscle inhibitory neurotransmission. 1156 Sep 40

Two-pore domain K(+) (K(2P)) channels are a new channel family. The goal of this study was to determine if K(2P) channels are activated by the nitric oxide (NO)/cGMP/PKG pathway in vascular smooth muscle. Relative levels of message for K(2P) channels were assessed in rat middle cerebral arteries (MCAs) using quantitative RT-PCR, and K(+) currents were measured in freshly dispersed vascular smooth muscle cells of the MCA. The rat MCA expresses a number of K(2P) channels. Message for TREK-1 was the most abundant K(2P) channel, followed by TASK-1 and TWIK-2, which were expressed at approximately 10% of the level of TREK-1. Message for other K(2P) channels was 1% or less than that of TREK-1. A number of K(2P) channels, including TREK-1, TWIK-2, and TASK-1, have putative PKG phosphorylation sites in the intracellular domains. The NO donor sodium nitroprusside (100 muM) or the membrane permeable analog of cGMP 8-bromo-cGMP (10 muM) elicited transient increases in whole cell current of vascular smooth muscle from the rat MCA. However, after large-conductance Ca(2+)-activated K(+) channels had been blocked with 10 mM tetraethylammonium (TEA), no increase in whole cell current was observed. Since K(2P) channels are resistant to the blocking effects of TEA, we conclude that K(2P) channels in vascular smooth muscle were not activated by the NO/cGMP/PKG pathway. Although K(2P) channels are highly expressed, K(2P) currents are not activated via the NO/cGMP pathway in rat MCA smooth muscle, despite the presence of numerous putative PKG phosphorylation sites.
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PMID:cGMP does not activate two-pore domain K+ channels in cerebrovascular smooth muscle. 1936 37