Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.1.4.3 (phospholipase C)
18,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The neuropeptide galanin potently inhibits insulin release, hippocampal acetylcholine release and firing of locus coeruleus cells, and stimulates feeding and release of growth hormone. Galanin regulates K+ channels, adenylyl cyclase and phospholipase C by acting at Gi/Go protein-coupled high-affinity receptors. Galanin receptor agonists such as the N-terminal fragment galanin1-16 act synergistically with morphine in the somatosensory system and have potential analgetic application. Galanin antagonists may be useful therapeutic agents in endocrinology, neurology and psychiatry. The enhancing effect of such agents on hippocampal cholinergic function would be useful in treatment of Alzheimer's disease. Recent synthesis of a series of high-affinity galanin antagonists, reviewed, along with galanin's actions, by Tamas Bartfai and colleagues, opens the possibility of examining the functions of endogenous galanin and test the pharmacological usefulness of antagonism of galanin function in the endocrine, somatosensory and central nervous systems.
...
PMID:Galanin and galanin antagonists: molecular and biochemical perspectives. 138 14

Growth Hormone has recently been shown to stimulate the formation of diacylglycerol in Ob1771 mouse preadipocyte cells without increasing inositol lipid turnover. Addition of growth hormone to Ob1771 cells prelabelled with [3H]glycerol or [3H]choline led to a rapid, transient and stoechiometric formation of labelled diacylglycerol and phosphocholine, respectively. In contrast, no change was observed in the level of choline and phosphatidic acid whereas the release of water-soluble metabolites in [3H]ethanolamine prelabelled cells exposed to growth hormone was hardly detectable. Stimulation by growth hormone of cells prelabelled with (2-palmitoyl 9, 10 [3H])phosphatidylcholine also induced the production of labelled diacyglycerol. Pertussis toxin abolished both diacylglycerol and phosphocholine formation induced by growth hormone. It is concluded that growth hormone mediates diacylglycerol production in Ob1771 cells by means of phosphatidylcholine breakdown involving a phospholipase C which is likely coupled to the growth hormone receptor via a pertussis toxin-sensitive G-protein.
...
PMID:Diacylglycerol production induced by growth hormone in Ob1771 preadipocytes arises from phosphatidylcholine breakdown. 212 19

To determine whether growth hormone (GH) directly stimulates insulin-like growth factor I (IGF I) gene expression in renal collecting duct, plasma membranes prepared from collecting ducts isolated from rat kidney, and collecting ducts themselves were incubated in presence and absence of GH. GH enhanced phospholipase C activity in collecting duct plasma membranes establishing the potential for GH-signal transduction. Inclusion of GH in suspensions of collecting ducts increased production of immunoreactive IGF I in a time-dependent and concentration-dependent manner. Production was stimulated significantly by addition of 10(-10), 10(-8), or 10(-6) M GH to suspensions for 2 h. IGF I produced in isolated collecting ducts was released into the suspending media. Levels of IGF I mRNA in collecting ducts were increased 2.8-fold after incubation with 10(-6) M GH in vitro. IGF I of collecting duct origin was indistinguishable from recombinant human IGF I in terms of its size and receptor-binding characteristics. Our findings demonstrate a direct action of GH to enhance collecting duct IGF I gene expression in vitro. Such enhancement is likely to reflect the mechanism by which GH stimulates renal IGF I production in intact kidney.
...
PMID:Growth hormone stimulates IGF I gene expression in isolated rat renal collecting duct. 239 72

To delineate pathways for "signal" transduction by growth hormone (GH) in proximal tubule, we incubated basolateral membranes isolated from canine kidney with human growth hormone (hGH) or human prolactin (hPrl) and measured levels of inositol trisphosphate (InsP3) in suspensions and of diacylglycerol extractable from the membranes. Incubation with hGH, but not hPrl, increased levels of InsP3 and diacylglycerol in a concentration-dependent manner. Half-maximal effects occurred between 0.1 and 1 nM hGH. Increased levels of InsP3 were measured after as little as 5 sec of incubation with 1 nM hGH, and increase was maximal after 15 sec. Increases were no longer detectable after 60 sec because of dephosphorylation of InsP3 in membrane suspensions. hGH did not affect rates of dephosphorylation. hGH-stimulated increases in InsP3 were detectable in membranes suspended in 0, 0.1, and 0.2 mM calcium but not in 0.3 or 1.0 microMs calcium. 125I-labeled hGH-receptor complexes with Mr values of 66,000 and 140,000 were identified in isolated basolateral membranes. Our findings establish that GH activates phospholipase C (phosphatidylcholine cholinephosphohydrolase, EC 3.1.4.3) in isolated canine renal proximal tubular basolateral membranes, potentially after binding to a specific receptor. This process could mediate "signal" transmission by GH across the plasma membrane of the proximal tubular cell and elsewhere.
...
PMID:Growth hormone activates phospholipase C in proximal tubular basolateral membranes from canine kidney. 278 86

Receptors for human, simian, ovine, bovine and murine prolactin, human growth hormone and human placental lactogen have been identified in plasma-membrane-containing subcellular particles isolated from rabbit mammary glands. The association and dissociation of (125)I-labelled prolactin are time- and temperature-dependent processes, both being maximal at 37 degrees C. (125)I-labelled prolactin prepared by the enzymic iodination procedure with lactoperoxidase binds better to receptors than does the preparation obtained by using chloramine-t as the oxidizing agent. The binding of (125)I-labelled prolactin to receptors is strongly influenced by pH and ionic composition but not by many low-molecular-weight compounds tested, e.g. steroids, nucleotides and several drugs. Receptor activity is sensitive to trypsin and phospholipase C digestion, suggesting that protein and phospholipid moieties are essential for the binding of (125)I-labelled prolactin. The binding of (125)I-labelled prolactin to receptors is a saturable and reversible process. Scatchard and Lineweaver-Burk analyses suggest that (125)I-labelled prolactin has a high affinity for its receptor. Binding of (125)I-labelled prolactin to receptors does not result in the destruction of the hormone. Considerable prolactin-binding activity is also observed in subcellular fractions isolated from the adrenal gland, liver, ovary and kidney of the pregnant rabbit, a finding that is consistent with other reported actions of prolactin in these organs.
...
PMID:Properties of a prolactin receptor from the rabbit mammary gland. 437 64

Bromocriptine or other dopamine agonists are usually effective for the treatment of prolactin-secreting adenomas. Five to 18% of prolactinomas, however, do not respond to such therapy. We have shown previously that such resistance to bromocriptine correlates with reduced binding to the D2 receptor subtype of dopamine, the major PRL inhibiting factor. In the present work, we demonstrated that reduced binding actually corresponds to decreased expression of the gene coding for the D2 receptor in the pituitary from bromocriptine-resistant patients, as shown by 4-fold lower levels of the corresponding mRNAs compared to those coding for actin. The existence of two D2 receptor isoforms, D2S and D2L generated by alternative splicing, has been described in several tissues, including the pituitary. Both are negatively coupled to adenylyl cyclase and inhibit prolactin secretion, but, in addition, the shortest one (D2S) is more efficiently coupled to phospholipase C. Consequently, we also investigated whether expression of a particular D2 receptor isoform was preferentially affected in resistant adenomas. The proportion of messengers corresponding to the short receptor isoform (D2S) was lower in resistant compared to responsive adenomas: D2S/D2L = 0.74 +/- 0.08 and 1.00 +/- 0.07, respectively. In parallel, much lower levels of D2 receptor mRNAs were found in growth hormone-secreting adenomas, with a D2S/D2L ratio comparable to those of both normal human pituitary and bromocriptine-sensitive prolactinomas (1.05 +/- 0.11). Thus, resistance to bromocriptine therapy seems to involve defects in D2 dopamine receptor expression and possibly in posttranscriptional splicing.
...
PMID:Decreased expression of the two D2 dopamine receptor isoforms in bromocriptine-resistant prolactinomas. 796 90

The parathyroid hormone (PTH)/parathyroid hormone-related peptide (PTHrP) receptor belongs to a newly discovered family of G protein-coupled receptors. Members of this family, which have been isolated from mammals, include the receptors for PTH/PTHrP, calcitonin, secretin, growth hormone-releasing hormone, vasoactive intestinal polypeptide (types 1 and 2), gastric-inhibitory polypeptide, glucagon-like peptide 1, glucagon, corticotropin-releasing factor, and the pituitary adenylate cyclase-activating peptide. Very recently, a receptor with remarkable homology to these mammalian receptors was isolated from the insect Manduca sexta, which indicates considerable conservation of these related proteins during evolution. Thus far the cognate ligands for these receptors are 27- to 46-amino-acid residues in length. Members of this novel receptor family are characterized by seven membrane-spanning domains and at least two conserved sites for N-linked glycosylation. Furthermore, 48-amino-acid residues, including eight extracellular cysteines, are identical in all receptors, and many other residues are highly conserved. The PTH/PTHrP receptor is expressed in a large variety of fetal and adult tissues, binds two ligands (PTH and PTHrP) with high affinity, and activates at least two second-messenger systems (adenylate cyclase and phospholipase C).
...
PMID:Molecular cloning and characterization of a parathyroid hormone/parathyroid hormone-related peptide receptor: a member of an ancient family of G protein-coupled receptors. 807 40

Hormone replacement should provide a serum hormone profile similar to that found in normal physiology. This is generally impractical because hormones are usually released episodically and therefore require frequent administration. However, rather than replacing the hormone directly, in theory, one could administer a mimic or amplifier of the pulse generator that controls pulsatile release of the particular hormone. Using growth hormone (GH) as a paradigm we sought such a mimetic that would provide episodic GH release when administered by the oral route. A GH secretagogue MK0677, is described that has these ideal properties; following oral administration MK0677 amplifies episodic GH release. Mechanistically, it synergizes with growth hormone releasing hormone (GHRH) through a receptor and signal transduction pathway distinct from that of GHRH and is a functional antagonist of somatostatin (SRIF). MK0677 also acts on the arcuate nucleus and appears to stimulate GHRH release. By using 35S-MK0677, a new G-protein coupled receptor for MK0677 was characterized in the plasma membrane fraction of pituitary and hypothalamic tissue. The receptor is present in very low abundance and couples to phospholipase C. Other ligands selective for this receptor also cause synchronization of well-defined pathways leading to GH release. Repeated oral treatment of dogs once daily with MK0677 initiates amplified pulsatile GH release accompanied by increases in IGF-1 that are sustained. The unique biological properties of MK0677 and other synthetic ligands that bind to the same receptor force us to predict that these ligands mimic a naturally occurring hormone that regulates pulsatile GH release. Understanding the regulatory mechanisms involved in this paradigm has broad implications for the control of pulsatile rhythms in the endocrine system.
...
PMID:Modulation of pulsatile GH release through a novel receptor in hypothalamus and pituitary gland. 870 Oct 83

Endothelins (ETs) were initially thought to be primarily involved in the control of cardiovascular activity, but the presence of ETs and their receptors in a wide variety of other tissues has suggested a much broader range of functions. Specific receptors for ETs are found in nonvascular tissues including neuronal, neuroendocrine, and endocrine cells. In addition, immunoreactive ETs are present in the brain, pituitary, and peripheral endocrine tissues. However, the ET levels in hypothalamo-hypophysial portal and peripheral blood are low, suggesting that the ET system participates in neuroendocrine regulation through paracrine and/or autocrine mechanisms. Both ETA and ETB receptors are expressed in the hypothalamus, adrenal, parathyroid glands, pancreas, ovary, uterus, placenta, and prostate, while only ETA receptors are expressed in GT1 neurons, anterior pituitary cells, alpha T3-1 immortalized gonadotropes, parathyroid-derived cells, thyrocytes, testicular Leydig and Sertoli cells, normal and neoplastic ovarian granulosa cells, chondrocytes, and other cell types. Activation of ET receptors elicits the sequence of cellular events typical of Ca(2+)-mobilizing receptors, with prominent increases in phosphoinositide hydrolysis and elevations of [Ca2+]i that occur in oscillatory and nonoscillatory modes depending on the cell type. ET-induced activation of the phosphoinositide/Ca(2+)- mobilizing pathway in neuronal and endocrine cells is associated with rapid stimulation of secretory responses, including release of gonadotropin-releasing hormone, oxytocin, vasopressin, substance P, atrial natriuretic peptides, gonadotropins, thyrotropin, growth hormone, parathyroid hormone, aldosterone, and catecholamines. On the other hand, ET has inhibitory actions on prolactin, progesterone, and renin release. In addition to stimulating phospholipase C-dependent pathways, ETs also activate phospholipase D-and MAP-kinase-dependent pathways in some of their target cells, as well as expression of early response genes and increased mitogenic activity. In many neuroendocrine cells, ET induces rapid and marked desensitization of its signaling system, in association with extensive internalization of ET receptors and reduced signaling and secretory responses. These findings raise the possibility that ETs participate in the control of secretory responses in the hypothalamo-pituitary system and peripheral endocrine cells, as well as in long-term aspects of regulation in certain neuroendocrine cells.
...
PMID:Expression and signal transduction pathways of endothelin receptors in neuroendocrine cells. 881 99

In goldfish, maturational gonadotropin (GTH) and growth hormone (GH) release are stimulated by two native GTH-releasing hormones (sGnRH and cGnRH-II). Both GnRHs stimulate GTH and GH release via activation of phospholipase C, protein kinase C, Ca2+ entry through voltage-sensitive channels and calmodulin. However, sGnRH-induced GTH release also involves arachidonic acid and intracellular Ca2+ components absent from its action on GH, as well as from cGnRH-II action on GTH and GH secretion. The relative roles and interactions of these signaling pathways in mediating sGnRH and cGnRH-II action on acute and prolonged GTH and GH release are compared. How two GnRHs bind to similar receptors but induce similar and dissimilar transduction mechanisms in two cell types and within one cell type is unknown.
...
PMID:GnRH signaling in goldfish pituitary cells. 883 90


1 2 3 4 Next >>

---