Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.11.18 (MAP)
 7,412 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cardiovascular effects of the IV infusion of TRH were studied in the rat. TRH tended to increase the MAP and markedly increased the CBF(tot) in the control group, in vagotomized animals and in methylatropine-pretreated rats. A marked vasodilation was noted in the pancreas, gastric mucosa, duodenum and cardiac muscle. This effect was turned to vasoconstriction, the heart excluded, in vagotomized animals. Muscarinic blockade attenuated the vasodilating effect of TRH in the duodenum and gastric mucosa. The results indicate that TRH elicits cerebral vasodilation and a partly nonmuscarinic parasympathetically mediated vasodilation in several gastrointestinal organs in parallel with a vasoconstriction which is unmasked by vagotomy.
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PMID:Cerebral and peripheral blood flow effects of TRH in the rat--a role of vagal nerves. 251 18

The enzymatic activity of mitogen-activated protein kinases (MAP kinases) increases in response to agents acting on a variety of cell surface receptors, including receptors linked to heterotrimeric G proteins of the Gi and Gq family. Recently, it has been shown that stimulation of beta-adrenergic receptors, which are typical of those that act through Gs to activate adenylyl cyclases, potently activates MAP kinases in the heart, resulting in the hypertrophy of the cardiac muscle (Lazou, A., Bogoyevitch, M.A., Clerk, A., Fuller, S.J., Marshall, C.J., and Sudgen, P.H. (1994) Circ. Res. 75, 938-941). We have observed that exposure of COS-7 cells to a beta-adrenergic agonist, isoproterenol, raises intracellular levels of cAMP and effectively activates protein kinase A (PKA) and an epitope-tagged MAP kinase. However, MAP kinase stimulation by isoproterenol was neither mimicked by expression of an activated mutant of G alpha s, nor by treatment with PKA-stimulating agents. Moreover, pretreatment of COS-7 with a permeable cAMP analog, 8-Br-cAMP, markedly decreased MAP kinase activation by either isoproterenol or epidermal growth factor. Thus, in COS-7 cells cAMP and PKA do not appear to mediate MAP kinase activation by beta-adrenergic receptors. Signaling from beta-adrenergic receptors to MAP kinase was inhibited by transfection of a chimeric molecule consisting of the CD8 receptor and the carboxyl terminus of the beta-adrenergic receptor kinase, which includes the beta gamma-binding domain. MAP kinase activation by isoproterenol was not affected by depletion of protein kinase C, but it was completely abolished by expression of Ras-inhibiting molecules. We conclude that signaling from beta-adrenergic receptors to MAP kinase involves an activating signal mediated by beta gamma subunits acting on a Ras-dependent pathway and a G alpha s-induced inhibitory signal mediated by cAMP and PKA. The balance between these two opposing mechanisms of regulation would be expected to control the MAP kinase response to beta-adrenergic agonists as well as to other biologically active agents known to act on Gs coupled receptors, including a number of hormones, neurotransmitters, and lipid mediators.
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PMID:Dual effect of beta-adrenergic receptors on mitogen-activated protein kinase. Evidence for a beta gamma-dependent activation and a G alpha s-cAMP-mediated inhibition. 755 65

Sodium nitroprusside (SNP) induces apoptosis in H9C2 cardiac muscle cells. Treatment with an exogenous NO donor SNP (2 mM) to H9C2 cells resulted in apoptotic morphological changes; a bright blue-fluorescent condensed nuclei and chromatin fragmentation by fluorescence microscope of Hoechst 33258-staining. The activity of caspase-3 like protease was increased during SNP-induced cell death. However, the activity of caspase-1 like protease was not affected by SNP. Pretreatment with Z-VAD-FMK (a pan-caspase inhibitor) or Ac-DEVD-CHO (a specific caspase-3 inhibitor) abrogated the SNP-induced cell death. SNP markedly activated three MAP kinases (JNK/SAPK, ERK and p38 MAP kinase) in the cardiac muscle cells. In this study, selective inhibition of the ERK or p38 MAPK pathway (by PD98059 or SB203580, respectively) had no effect on the extent of SNP-induced apoptosis in cardiac muscle cells. In contrast, inhibition of the JNK pathway by transfection of a dominant negative mutant of JNK markedly reduced the extent of SNP-induced cell death. Taken together, we suggest that JNK/SAPK will be related to SNP-induced apoptosis of H9C2 cardiac muscle cells.
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PMID:Sodium nitroprusside induces apoptosis of H9C2 cardiac muscle cells in a c-Jun N-terminal kinase-dependent manner. 1137 51

Alterations in the degree of the phosphorylation of ERKI/2, Akt-1 and p70 S6K in mouse skeletal and cardiac muscle was examined in vivo following an intraperitoneal injection of des IGF-I. Plasma levels of insulin, IGF-I and glucose were measured. The administration of des IGF-I had no effect on plasma levels of insulin, or IGF-I, but plasma glucose levels were decreased about 50% (p < 0.01). In both skeletal and cardiac muscle, des IGF-I increased the phosphorylation of Akt-1 at Ser 473 (p < 0.01) with no change in the phosphorylation of p44 and p42 MAP kinases at Thr202/Tyr204. The phosphorylation of p70 S6K at Thr421/Ser424 was increased in skeletal muscle (p < 0.01), but not in cardiac muscle. The phosphorylation of the nuclear transcription factor CREB phosphorylation at Ser 133 was not significantly changed in either skeletal or cardiac muscle. Des IGF-I increased the phosphorylation of the transcription factor FKHR in cardiac muscle only (p < 0.05). These data demonstrate that the administration of des IGF-I had differential effects on the activation of the MAP kinase and PI 3-kinase pathways in mouse skeletal and cardiac muscle.
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PMID:Differential effects of des IGF-1 on Erks, AKT-1 and P70 S6K activation in mouse skeletal and cardiac muscle. 1219 Jan 9