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

Na+, K+-ATPase activity of homogenates prepared from cauda epididymal golden hamster sperm increased after the addition of cGMP (50 microM), monobutyryl cGMP (0.5 microM) or cGMP-dependent protein kinase (0.94 micrograms/ml). Addition of monobutyryl cAMP (0.5 microM) or purified catalytic subunit of cAMP-dependent protein kinase (1.26 micrograms/ml) inhibited the activity of the Na+, K+-ATPase. Preincubation with a partially purified preparation of cAMP-dependent protein kinase inhibitor (75 micrograms/ml) stimulated the activity of the Na+, K+-ATPase, and this stimulation was decreased by the addition of 5 microM monobutyryl cAMP. It is not yet known whether direct and/or indirect mechanisms are involved, but these results are the first to describe such opposing effects by cyclic nucleotide-mediated processes on a Na+, K+-ATPase activity.
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PMID:Initial evidence for the modification of hamster sperm Na+, K+-ATPase activity by cyclic nucleotide-mediated processes. 630 96

Passage of spermatozoa through the epididymis is obligatory for sperm maturation processes and is based on spontaneous phasic contractions (SC) of the epididymal duct. Here, the functional role of cyclic GMP (cGMP) signaling in modulating SC in the bovine epididymal caput and corpus region was examined by muscle tension recording and immunological and autoradiographic techniques. The cGMP-analog 8-bromo (Br)-cGMP, as well as the nitric oxide (NO) donor sodium nitroprusside and the natriuretic peptides (NPs) atrial NP and C-type NP, displayed distally increasing SC-relaxant effects. In agreement, a distally increasing epididymal expression of the cGMP-dependent protein kinase I (PKG I), endothelial NO synthase (eNOS), and the atrial NP receptor was found. Immunoreactivity for PKG, soluble guanylate cyclase, and eNOS could be localized to the epididymal muscle cells as well as to the epithelial basal cells only at the corpus level. The SC-relevant action of NO and the NPs was cGMP dependent, and the action of 8-Br-cGMP, in turn, was modified by epithelial and luminal factors. The NOS inhibitor L-NAME (N(omega)-nitro-L-arginine methyl ester) caused an increase in SC frequency, indicating basal activity of NO generating enzymes. The SC-inhibitory effect of 8-Br-cGMP was clearly reduced by the PKG inhibitor Rp-8-Br-cGMPS as well as by iberiotoxin, thapsigargin, and indomethacin, pointing to PKG as main SC-relevant target of cGMP, and to large-conductance calcium-activated K(+) channels, the sarcoplasmic-endoplasmic reticulum Ca(2+)-ATPase and cyclooxygenase-1 as possible targets of PKG. These data support an essential role of cGMP signaling in the control of epididymal peristalsis, thereby enabling fine tuning of sperm transport and maturation.
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PMID:Regulation of spontaneous contractile activity in the bovine epididymal duct by cyclic guanosine 5'-monophosphate-dependent pathways. 1643 52

This study investigated the effects of 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1), a soluble guanylyl cyclase (sGC) activator and potential antithrombotic agent, on lipolysis in isolated visceral fat cells of the rat. Visceral fat cells were isolated from epididymal fat pads of rats and treated with YC-1 at different doses and times. Glycerol release, and intracellular cAMP and cGMP levels were analyzed by specific kits. Moreover, several inhibitors or drugs were used to examine the signal transduction pathways of YC-1-induced lipolysis in adipocytes. Herein we report that YC-1 stimulated glycerol release in dose- and time-dependent manners. Intracellular cAMP and cGMP levels of adipocytes both increased in time-dependent manners, but elevation of the cGMP level was faster and higher than that of the cAMP level after YC-1 treatment. An sGC inhibitor (ODQ) inhibited YC-1-induced glycerol release, indicating the involvement of sGC in YC-1-induced lipolysis. Administration of insulin, an activator of type-3B phosphodiesterase (PDE-3B), attenuated YC-1-induced lipolysis, indicating that elevation of the cAMP level is an important step in the lipolytic effect of YC-1. In addition, YC-1-induced lipolysis was inhibited by a protein kinase A (PKA) inhibitor (KT5720) but not by a PKG inhibitor (KT5823), indicating that YC-1-induced lipolysis occurs through a PKA-dependent pathway. A Western blot analysis showed that extracellular signal-regulated kinase was not phosphorylated by YC-1 treatment. In conclusion, our results suggest that YC-1 might stimulate lipolysis via activation of sGC/cGMP and then activation of the cAMP/PKA signaling cascade in isolated rat visceral adipocytes.
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PMID:YC-1, a potent antithrombotic agent, induces lipolysis through the PKA pathway in rat visceral fat cells. 2265 14

Lipid metabolism in visceral fat cells is correlated with metabolic syndrome and cardiovascular diseases. Okadaic-acid, a 38-carbon fatty acid isolated from the black sponge Halichondria okadai, can stimulate lipolysis by promoting the phosphorylation of several proteins in adipocytes. However, the mechanism of okadaic acid-induced lipolysis and the effects of okadaic acid on lipid-droplet-associated proteins (perilipins and beta-actin) remain unclear. We isolated adipocytes from rat epididymal fat pads and treated them with isoproterenol and/or okadaic acid to estimate lipolysis by measuring glycerol release. Incubating adipocytes with okadaic acid stimulated time-dependent lipolysis. Lipid-droplet-associated perilipins and beta-actin were analyzed by immunoblotting and immunofluorescence, and the association of perilipin A and B was found to be decreased in response to isoproterenol or okadaic acid treatment. Moreover, okadaic-acid treatment could enhance isoproterenol-mediated lipolysis, whereas treatment of several inhibitors such as KT-5720 (PKA inhibitor), calphostin C (PKC inhibitor), or KT-5823 (PKG inhibitor) did not attenuate okadaic-acid-induced lipolysis. By contrast, vanadyl acetylacetonate (tyrosine phosphatase inhibitor) blocked okadaic-acid-dependent lipolysis. These results suggest that okadaic acid induces the phosphorylation and detachment of lipid-droplet-associated perilipin A and B from the lipid droplet surface and thereby leads to accelerated lipolysis.
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PMID:Okadaic Acid, a Bioactive Fatty Acid from Halichondria okadai, Stimulates Lipolysis in Rat Adipocytes: The Pivotal Role of Perilipin Translocation. 2431 76