Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

ACTH is known to act through the activation of cAMP/PKA in adrenocortical cells, but it has been suggested that it could also act via other pathways such as the ERK 1/2 cascade. To determine the effects of ACTH administration at sequential time points on the activation of ERKs 1/2, groups of rats (n = 6/group) were subjected to i.p. injections of either ACTH (Synacthen Depot-0.2 mg/Kg), or saline (Ct). The animals were sacrificed and the adrenal glands collected at different timings after ACTH injection (2 h, 18 h and 24 h). Two additional groups were injected daily until sacrifice (3 days and 15 days). Blood was collected for analysis and the adrenals were used for immunohistochemistry or Western Blot (WB) analysis. Immunoreactivity was scored by counting the mean number of zonae fasciculata (ZF) and reticularis (ZR) positive cells/section (mean +/- SEM). Adrenal weight was increased by ACTH in comparison with Ct. Corticosterone levels, as expected, were higher in ACTH treated animals than in Ct. The number of pERK positive cells increased in a time-dependent manner until 3d, and declined although not significantly in the 15 days animals (Control--48.13 +/- 9.0; ACTH 2 h--125.93 +/- 14.5; ACTH 18 h-139.46 +/- 10.0; ACTH 24 h--185.28 +/- 13.3; ACTH 3 days--198.47 +/- 18.6; ACTH 15 days--158.58 +/- 15.1). Comparable results were obtained with WB analysis. Our data shows that ACTH induces the activation of the MAPK/ERKs 1/2 cascade, especially in the ZF, consistent with this zone being more responsive to ACTH.
 ...
PMID:ACTH modulates ERK phosphorylation in the adrenal gland in a time-dependent manner. 1566 9

Telokin, a 17 kDa smooth muscle specific protein, consists of the C-terminal domain of MLCK, is phosphorylated by PKA and PKG at Ser13 in vivo (Wu et al. (1998) J Biol Chem 273: 11362-11369; Walker et al. (2001) J. Biol Chem 276: 24519-24524) and is proposed to induce Ca2+-desensitization through activation of myosin phosphatase (Wu et al. (1998) J. Biol Chem 273: 11362-11369). Telokin is reported to be highly expressed in phasic with only trace amounts in tonic smooth muscle. In alpha-toxin permeabilized femoral artery, 5 microM 8-Br-cGMP induced a two-fold increase in telokin phosphorylation and a maximal 30% relaxation of Ca2+-activated force compared to a 90% relaxation in phasic ileum muscle consistent with the relative amounts of telokin expressed in ileum, 27+/-4.6 microM SEM compared to 6+/-1.7 microM SEM, in femoral artery. Recombinant Wt telokin and the phospho-telokin mutant, S13D relaxed telokin-depleted femoral artery, by 38+/-8% SEM and 60+/-20% SEM, respectively. 8-Br-cGMP increased the rate and decreased the amplitude of force development initiated by photolysis of caged ATP in alpha-toxin permeabilized ileum and femoral artery smooth muscle, consistent with a cGMP-induced increase in phosphatase activity. Similarly, in telokin depleted ileum, recombinant S13D mutant telokin significantly increased the rate (0.08+/-0.01 s-1 vs. 014+/-0.02 s-1) and decreased force amplitude. In conclusion, our data support a role for telokin in cyclic nucleotide-induced relaxation of not only phasic, but also tonic smooth muscle and that this relaxation is mediated by activation of myosin phosphatase activity leading to a decrease in myosin light chain phosphorylation.
 ...
PMID:Telokin mediates Ca2+-desensitization through activation of myosin phosphatase in phasic and tonic smooth muscle. 1575 Aug 50

GABAergic inhibitory transmission is very abundant within the insect brain. We, therefore, studied the functional properties of the ionotropic GABA receptor of honeybee mushroom body Kenyon cells in vitro. GABA applications elicit rapidly activating and desensitizing currents, which are concentration-dependent between 10 and 500 microM. The mean peak amplitude induced by 500 microM GABA at a holding potential of -110 mV is -1.55 +/- 0.23 nA (SEM, n = 29). The GABA-induced current is mediated by Cl(-) ions because (1) the reversal potential of the GABA-induced current of -40.6 mV is very close to the calculated Nernst potential of chloride (-44.8 mV). (2) With equimolar chloride concentrations the reversal potential shifted to about 0 mV. GABA or muscimol are equally efficient channel agonists, whereas CACA is a partial agonist. Picrotoxin or philanthotoxin (100 microM) completely and reversibly block the GABA-induced current, bicuculline (100 microM) has no effect. Elevating the intracellular Ca(2+) concentration increases the GABA current amplitude. This modulatory effect is blocked by the kinase blocker K 252a, but not by blockers of CaMkinaseII (KN-93), PKC (bisindolylmaleimide) or PKA (KT 5720). We conclude that Kenyon cells express functional GABA receptors whose properties support an inhibitory role of GABAergic transmission.
 ...
PMID:An ionotropic GABA receptor in cultured mushroom body Kenyon cells of the honeybee and its modulation by intracellular calcium. 1818 Sep 28

Glucagon-like peptide-1 (GLP-1) is a proglucagon-derived hormone with cellular protective actions. We hypothesized that GLP-1 would protect the endothelium from injury during inflammation. Our aims were to determine the: (1) effect of GLP-1 on basal microvascular permeability, (2) effect of GLP-1 on increased microvascular permeability induced by lipopolysaccaride (LPS), (3) involvement of the GLP-1 receptor in GLP-1 activity, and (4) involvement of the cAMP/PKA pathway in GLP-1 activity. Microvascular permeability (L(p)) of rat mesenteric post-capillary venules was measured in vivo. First, the effect of GLP-1 on basal L(p) was measured. Second, after systemic LPS injection, L(p) was measured after subsequent perfusion with GLP-1. Thirdly, L(p) was measured after LPS injection and perfusion with GLP-1+GLP-1 receptor antagonist. Lastly, L(p) was measured after LPS injection and perfusion with GLP-1+inhibitors of the cAMP/PKA pathway. Results are presented as mean area under the curve (AUC)+/-SEM. GLP-1 had no effect on L(p) (AUC: baseline=27+/-1.4, GLP-1=1+/-0.4, p=0.08). LPS increased L(p) two-fold (AUC: LPS=54+/-1.7, p<0.0001). GLP-1 reduced the LPS increase in L(p) by 75% (AUC: LPS+GLP-1=34+/-1.5, p<0.0001). GLP-1 antagonism reduced the effects of GLP-1 by 60% (AUC: LPS+GLP-1+antagonist=46+/-2.0, p<0.001). The cAMP synthesis inhibitor reduced the effects of GLP-1 by 60% (AUC: LPS+GLP-1+cAMP inhibitor=46+/-1.5, p<0.0001). The PKA inhibitor reduced the effects of GLP-1 by 100% (AUC: LPS+GLP-1+PKA inhibitor=56+/-1.5, p<0.0001). GLP-1 attenuates the increase in microvascular permeability induced by LPS. GLP-1 may protect the endothelium during inflammation, thus decreasing third-space fluid loss.
 ...
PMID:Glucagon-like peptide-1 protects mesenteric endothelium from injury during inflammation. 1956 May

To better use wheat straw and minimize its negative impact on environment, a novel semi-interpenetrating polymer networks (semi-IPNs) superabsorbent resin (SAR) composed of wheat straw cellulose-g-poly (potassium acrylate) (WSC-g-PKA) network and linear polyvinyl alcohol (PVA) was prepared by polymerization in the presence of a redox initiating system. The structure and morphology of semi-IPNs SAR were characterized by means of FTIR, SEM and TGA, which confirmed that WSC and PVA participated in the graft polymerization reaction with acrylic acid (AA). The factors that can influence the water absorption of the semi-IPNs SAR were investigated and optimized, including the weight ratios of AA to WSC and PVA to WSC, the content of initiator and crosslinker, neutralization degree (ND) of AA, reaction temperature and time. The semi-IPNs SAR prepared under optimized synthesis condition gave the best water absorption of 266.82 g/g in distilled water and 34.32 g/g in 0.9 wt% NaCl solution.
 ...
PMID:Synthesis of wheat straw cellulose-g-poly (potassium acrylate)/PVA semi-IPNs superabsorbent resin. 2354 72