Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The external layer of the median eminence is comprised of nerve fibres that terminate on the primary plexus of the hypophysial portal vessels. This system is a unique neurovascular synapse which can be used as a window through which may be studied the characteristics of central neurotransmission. The heterogeneity of the neuropil of the external layer of the median eminence, in terms of neurotransmitter types, carries the advantage that interactions between different classes of neurons can be investigated. These points are illustrated by physiological and pharmacological studies on the release into hypophysial portal blood of several neuropeptides including luteinizing hormone releasing hormone, thyrotrophin releasing hormone, vasoactive intestinal peptide, somatostatin 14, 28 and (1-12) 28, vasopressin and oxytocin. The portal vessels convey these neurohormones to the anterior pituitary gland where they stimulate or inhibit the release of pituitary hormones. The way in which the pituitary gland may be used to investigate the "post synaptic" effects of neuropeptides is illustrated with special reference to luteinizing hormone releasing hormone. In addition to the "established" neurohormones, attention is also focused on a recently discovered hypothalamic pituitary system that controls the release of plasminogen activator and on thyrocalcitonin and the calcitonin gene related peptide which demonstrate the way in which studies of the hypothalamus have led to the discovery of new neural control mechanisms.
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PMID:The external layer of the median eminence: A neurovascular synapse. 2049 12

The sole FDA approved treatment for acute stroke is tissue type plasminogen activator (tPA). However, tPA potentiates impairment of pial artery dilation in response to hypotension after hypoxia/ischemia (H/I) in pigs. ATP and Ca sensitive K channels (Katp and Kca) are important regulators of cerebrovascular tone and mediate cerebrovasodilation in response to hypotension. Mitogen activated protein kinase (MAPK), a family of at least 3 kinases, ERK, p38 and JNK, is upregulated after H/I, with the ERK isoform contributing to vasodilator impairment. This study examined the effect of H/I on Katp and Kca induced pial artery dilation and the roles of tPA and ERK during/after injury in piglets equipped with a closed cranial window. H/I blunted vasodilation induced by the Katp agonists cromakalim, calcitonin gene related peptide (CGRP) and the Kca agonist NS 1619; the effect of each was exacerbated by tPA. Pre- or post-injury treatment with EEIIMD, a hexapeptide derived from plasminogen activator-1, and ERK antagonist U 0126 prevented Katp and Kca channel agonist induced vasodilator impairment while the inactive analogue EEIIMR had no effect. ERK was upregulated after H/I, which was potentiated by tPA. These data indicate that H/I impairs K channel mediated cerebrovasodilation. tPA augments loss of K channel function after injury by upregulating ERK. These data suggest that thrombolytic therapy for treatment of CNS ischemic disorders can dysregulate cerebrohemodynamics by impairing cation-mediated control of cerebrovascular tone.
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PMID:tPA contributes to impairment of ATP and Ca sensitive K channel mediated cerebrovasodilation after hypoxia/ischemia through upregulation of ERK MAPK. 2118 29

The sole Food and Drug Administration-approved treatment for acute stroke is tissue-type plasminogen activator (tPA), but tPA aggravates impairment of cerebrovasodilation during hypotension in a newborn pig photothrombotic model of stroke. Coupling to carrier red blood cells (RBC) enhances thrombolytic effects of tPA, while reducing its side effects. ATP- and Ca-sensitive K channels (Katp and Kca) are important regulators of cerebrovascular tone and mediate cerebrovasodilation during hypotension. Mitogen-activated protein kinase, a family of at least three kinases, ERK, p38, and c-Jun-N-terminal kinase (JNK), is upregulated after photothrombosis. This study examined the effect of photothrombosis on Katp- and Kca-induced cerebrovasodilation and the roles of tPA and JNK during/after injury. Photothrombosis blunted vasodilation induced by the Katp agonists cromakalim, calcitonin gene-related peptide, and the Kca agonist NS 1619, which was aggravated by injection of tPA. In contrast, both pre- or post-injury thrombosis injection of RBC-tPA and JNK antagonist SP 600125 prevented impairment of Katp- and Kca-induced vasodilation. Therefore, JNK activation in thrombosis impairs K channel-mediated cerebrovasodilation. Standard thrombolytic therapy of central nervous system ischemic disorders using free tPA poses the danger of further dysregulation of cerebrohemodynamics by impairing cation-mediated control of cerebrovascular tone, whereas RBC-coupled tPA both restores reperfusion and normalizes cerebral hemodynamics.
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PMID:RBC-coupled tPA Prevents Whereas tPA Aggravates JNK MAPK-Mediated Impairment of ATP- and Ca-Sensitive K Channel-Mediated Cerebrovasodilation After Cerebral Photothrombosis. 2357 46

A new strategy is developed to prepare porous microspheres with narrow size distribution for peptides controlled release, involving a fabrication of porous microspheres without any porogens followed by a pore closing process. Amphiphilic polymers with different hydrophobic segments (poly(monomethoxypolyethylene glycol-co-d,l-lactide) (mPEG-PLA), poly(monomethoxypolyethylene glycol-co-d,l-lactic-co-glycolic acid) (mPEG-PLGA)) are employed as microspheres matrix to prepare porous microspheres based on a double emulsion-premix membrane emulsification technique combined with a solvent evaporation method. Both microspheres possess narrow size distribution and porous surface, which are mainly caused by (a) hydrophilic polyethylene glycol (PEG) segments absorbing water molecules followed by a water evaporation process and (b) local explosion of microspheres due to fast evaporation of dichloromethane (MC). Importantly, mPEG-PLGA microspheres have a honeycomb like structure while mPEG-PLA microspheres have a solid structure internally, illustrating that the different hydrophobic segments could modulate the affinity between solvent and matrix polymer and influence the phase separation rate of microspheres matrix. Long term release patterns are demonstrated with pore-closed microspheres, which are prepared from mPEG-PLGA microspheres loading salmon calcitonin (SCT). These results suggest that it is potential to construct porous microspheres for drug sustained release using permanent geometric templates as new porogens.
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PMID:A novel strategy for the preparation of porous microspheres and its application in peptide drug loading. 2728 78


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