Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The liver plasma membrane Ca2+ pump is supposed to extrude cytosolic calcium out of the cell. This system has now been well defined on the basis of its plasma membrane origin, its high affinity Ca2+ -stimulated ATPase activity, its Ca2+ transport activity, its phosphorylated intermediate. The liver calcium pump appears to be a target of hormonal action since it has been shown that glucagon and calcium mobilizing hormones namely alpha 1-adrenergic agonists, vasopressin, angiotensin II inhibit this system. The present review details the mechanism of calcium pump inhibition by glucagon and points out its difference from the inhibition process induced by calcium mobilizing hormones. We conclude that the inhibitory action of the Ca2+ mobilizing hormones and glucagon on the liver plasma membrane Ca2+ pump might play a key role in the actions of these hormones by prolonging the elevation in cytosolic free Ca2+.
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PMID:The liver plasma membrane Ca2+ pump: hormonal sensitivity. 241 53

The quenching of fura-2 fluorescence by the influx of extracellular Mn2+ was measured to indicate the flux rates through receptor-operated calcium channels in the plasma membrane of rat hepatocytes. Neomycin, an inhibitor of phospholipase C, inhibited the vasopressin-induced influx of Mn2+. Thus, the agonist-induced entry of extracellular calcium into hepatocytes is linked to a phospholipase C-generated second messenger. Microinjection of inositol 1,3,4,5-tetrakisphosphate [Ins(1,3,4,5)P4], inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] or 3-deoxy-3-fluoro-Ins(1,4,5)P3 revealed that Ins(1,4,5)P3 rather than Ins(1,3,4,5)P4 is responsible for calcium entry. The activation of phospholipase C by vasopressin produced an influx of Mn2+ independent of the depletion of intracellular calcium stores if this depletion was delayed by the Ins(1,4,5)P3 receptor antagonist heparin or by the use of a low agonist concentration. Thapsigargin, an inhibitor of the store calcium pump, leading to an Ins(1,4,5)P3-independent emptying of stores, gave a short living signal (less than 3 min) for calcium entry. We propose that Ins(1,4,5)P3 is able to stimulate calcium entry by two pathways. (a) Ins(1,4,5)P3 activates receptor-operated calcium channels in a direct manner. The calcium entry resulting from this is followed (b) by the Ins(1,4,5)P3-induced depletion of calcium stores, producing a store-dependent entry.
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PMID:Inositol 1,4,5-trisphosphate activates receptor-mediated calcium entry by two different pathways in hepatocytes. 820 Mar 48

We have demonstrated in liver from male rats that both endothelin A (ETA) and ETB receptors coexist in equal proportion and that ETA receptors mediate a calcium-dependent activation of glycogenolysis. We describe here a sex difference in endothelin action in hepatocytes because, in female rats, 80% of the ET receptors are of ETB type and, accordingly, activation of glycogenolysis is an ETB-mediated process (EC50 = 0.03 pM). ET-1 stimulation of glycogenolysis in female rats was consecutive to activation of phosphatidylinositol 4,5-bisphosphate hydrolysis (EC50 = 0.03 pM) and to inhibition of the calcium extrusion pump (IC50 = 0.03 pM) in plasma membranes, with ET-1 approximately sarafotoxin S6C approximately ET-3. Endothelin regulation of each effector was potentiated by GTP gamma S. ET-1 did not stimulate adenylyl cyclase activity. To identify the nature of the guanine nucleotide regulatory proteins (G protein(s)) coupling ETB receptors to each effector, we used antibodies against the COOH terminus of different G protein alpha subunits. Antibodies reactive with Gs alpha (RM) blocked ET-1 inhibition of the calcium pump, while they did not affect ET-1 stimulation of phospholipase C. Antibodies reactive with Gq alpha (QL) dose-dependently antagonized stimulation of phospholipase C by ET-1 and vasopressin, without affecting ET-1 inhibition of the calcium pump. Antibodies reactive with Gi1 alpha/Gi2 alpha (AS) had no effect on either system. We conclude that the calcium signal provoked by endothelins in hepatocyte is not only consecutive to activation of phospholipase C but also to inhibition of the plasma membrane calcium pump, each effector being coupled to ETB receptors by different G proteins, Gq, and Gs.
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PMID:Coupling of endothelin B receptors to the calcium pump and phospholipase C via Gs and Gq in rat liver. 829 32

We previously demonstrated that the antiprogestogen RU 486, when superfused on myometrial strips, induces a rapid decrease in spontaneous uterine contractile frequency, an increase in amplitude and duration of contractions, and a concomitant decrease in 6-keto PGF(1alpha) release. In this study, we present further work on the role of calcium transients and the involvement of the PLC/PKC pathway in mediating RU 486 effects. We found no clear causal relationship between the spontaneous contractility controlled by external Ca++ concentration and 6-keto PGF(1alpha) release depending mostly on intracellular Ca++ mobilization. We show that RU 486 strengthened the inhibitory effect of TMB8, a potent inhibitor of internal calcium, on both spontaneous contractility and 6-keto PGF(1alpha), release and antagonized the stimulatory action of thapsigargin, a toxin blocking the endoplasmic reticulum calcium pump (ER Ca++ ATPase). These data indicate that RU 486 could act as an inhibitor of intracellular Ca++ mobilization. A slight but significant decrease of the prostanoid liberation was observed in the presence of U73122, an inhibitor of PLC, but not in the presence of neomycin, another PLC inhibitory compound. PKC inhibitors, staurosporine and H7 did not significantly affect spontaneous 6-keto PGF1alpha release, showing that PIP2 hydrolysis and PKC pathway were not involved in the basal release of the prostacyclin metabolite. Vasopressin (AVP), an agent known to induce contractility of the non-pregnant human uterus, markedly increased 6-keto PGF(1alpha) release in a dose-dependent manner. Stimulation of GTP-regulated proteins (G proteins) by ALF4 was accompanied by a rise in 6-keto PGF(1alpha) liberation and a high contractile activity. The effects of both vasopressin and ALF4- were not significantly opposed by RU 486, indicating that other sources of Ca++, not controlled by the steroid, were involved in the agonist-stimulated prostanoid release. Studies with structurally related RU 486 analogues showed that the steroid effects were not dependent on their antihormonal activity, but rather on a specific 11beta arylsubstitution and a 17beta-hydroxy-13beta-methyl configuration of the 4,9-estradien-3-one molecule.
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PMID:RU 38486 inhibits intracellular calcium mobilization and PGI2 release from human myometrium: mechanisms of action. 900 39

Insulin-like peptide 5 (INSL5) mRNA was detected in the mouse hypothalamus by RT-PCR. Immunohistochemical studies using an antiserum against the mouse INSL5 peptide revealed INSL5-immunoreactive (irINSL5) neurons in the paraventricular, supraoptic, accessory secretory, and supraoptic retrochiasmatic nuclei and immunoreactive cell processes in the internal layer of the median eminence. In the pituitary, irINSL5 was detected in terminal-like elements of the posterior lobe and in cells of the anterior lobe. Double-labeling experiments showed that irINSL5 is expressed in vasopressin-, but not oxytocin-containing neurons. INSL5 (100 nm) administered to dissociated and cultured mouse hypothalamic neurons elevated cytosolic calcium concentrations [Ca(2+)](i), as assessed by the microfluorimetric fura-2 method. In a Ca(2+)-free medium, INSL5 induced in dissociated neurons an increase of [Ca(2+)](i), which was sensitive to the endoplasmic reticulum calcium pump inhibitor thapsigargin (1 microm) and the IP(3) receptor blocker 2-aminoethoxydiphenyl borate (100 microm) or xestospongin C (5 microm). Our result provides the first evidence that INSL5 is expressed in a population of cells in the mouse hypothalamus and pituitary and that it elevates [Ca(2+)](i) by a mechanism involving both Ca(2+) influx and Ca(2+) release from intracellular stores. The concentration of irINSL5 in the hypothalamic-pituitary axis suggests a neuroendocrine function of this insulin superfamily member.
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PMID:Insulin-like peptide 5: expression in the mouse brain and mobilization of calcium. 1660 Nov 33