Cyclic GMP is common second messenger in a plethora of processes. Its major intracellular receptors are the cGMP-dependent protein kinases (PKGs). In this minireview we summarise the main results of studies on structure and physiological role of PKGs.
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This paper reviews studies that investigated mechanisms of the induction of long-term synaptic efficacy increase in local horizontal connections in slices of adult rat motor cortex. Long-term potentiation (LTP) could be induced by electrical stimulation of afferents using theta burst stimulation (TBS) conditionally, when synaptic inhibition was transiently blocked by focal application of GABAA receptor antagonist. Robust, long-lasting enhancement of synaptic transmission in horizontal connections was induced by brief application of the potassium channel blocker, tetraethylammonium (TEA, 25 mM), to the incubation medium. This TEA-LTP could be blocked by nifedipine, a voltage-dependent calcium channel blocker. A transient exposure of slices to elevated extracellular calcium (5 mM) resulted in a long-lasting enhancement of responses, termed Ca-LTP, which could be blocked by the antagonist of NMDA receptors, APV. The induction of both TEA-LTP and Ca-LTP, could be prevented by inhibitors of the extracellular signal regulated kinase (ERK) cascade U0126 and PD 98059. A transient activation of the ERK, 15 min after application of TEA or elevated [Ca2+], was demonstrated using immunofluorescence. Both forms of plasticity could also be prevented by the inhibitor of cAMP-dependent protein kinases (PKA), Rp-cAMPS. These studies indicate the involvement of the ERK and PKA signaling mechanisms in synaptic plasticity of the motor cortex in vitro. Since LTP in horizontal connections of the motor cortex has previously been shown to be related to the acquisition of a motor skill, it is suggested that the ERK and PKA signaling pathways may be involved in motor learning.
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Heparin is a highly sulfated glycosaminoglycan with many functions such as antilipemic and antithrombotic.In spite os these activities heparin is able to inhibit vacsular smooth muscle cells proliferation and mmigration what seems to be very important event in the pathogenesis of atherosclerosos.The molecular mechanism of the action of heparin on smooth muscle cells is not yet understood.Heparin inhibits growth factors binding to their receptors,oncogenes expressionand has influence on the extracellular matrix protein deposition in the artery wall.
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