Phosphoinositides, calcium

Oxytocin acts through G protein-coupled receptors and the phosphoinositide-calcium second-messenger system to contract uterine smooth muscle. Oxytocin also stimulates the release of prostaglandins and leukotrienes that augment uterine contraction. Oxytocin in small doses increases both the frequency and the force of uterine contractions. At higher doses, it produces sustained contraction. 

The characteristics of the four major classes of histamine receptors are summarized. Question marks indicate suggestions from the literature that have not been confirmed. AA, arachidonic acid DAG, diacylglycerol Iko,2+, calcium-activated potassium current IP3, inositol 1,4,5-trisphosphate NHE, sodium-proton exchange, PKC, protein kinase C NO, nitric oxide PTPLC, phosphoinositide-specific phospholipase C TXA2, thromboxane A2. Has brain-penetrating characteristics after systemic administration. 

In many cells, phosphoinositide signaling leads to an elevation in intracellular calcium levels through the release of calcium from intracellular stores in response to IP3-dependent gating of channels in the endoplasmic epithelium (Ch. 20). It is not known if IP3 plays a critical role in TRC transduction, but such a role would be consistent with recent findings that a Ca2+-activated cation channel, TRPM5, is essential for normal sweet, bitter and umami taste function [49,66-69],... 

Manna s data (1991) of the efficacy of a nimodipine and lithium combination are of particular interest in reference to the above hypotheses related to combined effects on calcium-related mechanisms. Lithium obviously exerts complex effects on a variety of systems in brain, but its effects on phosphoinositide turnover and cyclic adenosine monophosphate and downstream effects on 1,4,5-inositol triphosphate (IP3) metabolism in calcium-related processes (as reviewed by Berridge 1989 H. L. Meltzer 1990 and... 

Post et al. 1992) are also worthy of consideration. Effects on the IP3 receptor-mediated calcium release have also been shown to affect ultrarapid neuronal and cellular calcium oscillations in several different types of preparations, raising the possibility that IP3 modulation, either directly or indirectly through effects on phosphoinositide turnover, could be important to some elements of lithium s and related agents mood-stabilizing effects (Berridge 1989 Dixon et al. 1992 Lupu-Meiri et al. 1994 Varney et al. 

Hirvonen MR, Paljarri L, Naukkarinen A, et al Potentiation of malaoxon-induced convulsions by lithium early neuronal injury, phosphoinositide signaling and calcium. Toxicol Appl Pharmacol 104 276-289, 1990... 

Patel J, Keith RA, Salama AI, et al Role of calcium in regulation of phosphoinositide signaling pathway. J Mol Neurosci 3 1-9, 1991 Patil VJ Development of transient obsessive-compulsive symptoms during treatment with clozapine. Am J Psychiatry 149 272, 1992 Pato MT, Zohar-Kadouch R, Zohar J, et al Return of symptoms after discontinuation of CMl in patients with OCD. Am J Psychiatry 145 1521-1522, 1988 Pato PT, Pigott TA, Hill JL, et al Controlled comparison of buspirone and CMl in OCD. Am J Psychiatry 148 127-129, 1991 Patterson JF Treatment of acute mania with verapamil (letter). J Clin Psycho-pharmacol 7 206-207, 1987... 

Janmey, P.A. Phosphoinositides and calcium as regulators of cellular actin assembly and disassembly (1994) Ann. Rev. Physiol. 56,169-191... 

With its multiple second messengers and protein kinases, the phosphoinositide signaling pathway is much more complex than the cAMP pathway. For example, different cell types may contain one or more specialized calcium- and calmodulin-dependent kinases with limited substrate specificity (eg, myosin light-chain kinase) in addition to a general calcium- and calmodulin-... 

These and other nonreceptor elements of the calcium-phosphoinositide signaling pathway are of considerable importance in pharmacotherapy. For example, lithium ion, used in treatment of bipolar (manic-depressive) disorder, affects the cellular metabolism of phosphoinositides (see Chapter 29). 

The calcium-phosphoinositide and cAMP signaling pathways oppose one another in some cells and are complementary in others. For example, vasopressor agents that contract smooth muscle act by IP3-mediated mobilization of Ca2+, whereas agents that relax smooth muscle often act by elevation of cAMP. In contrast, cAMP and phosphoinositide second messengers act together to stimulate glucose release from the liver. 

The phosphoinositides constitute 2-8% of the lipid of eukaryotic cell membranes but are metabolized more rapidly than are other lipids.265 278 279 283 - 285 A simplified picture of this metabolism is presented in Fig. 11-9. Phosphatidylinositol is converted by the consecutive action of two kinases into phosphatidylinositol 4,5-bisphosphate.286287 The InsP3 released from this precursor molecule by receptor-stimulated phospholipase C is thought to mobilize calcium ions by... 

It was long thought that boron was not required by human beings, but more recent studies suggest that we may need 30 pg / day.d Tire possible functions are uncertain. Animals deprived of boron show effects on bone, kidney, and brain as well as a relationship to the metabolism of calcium, copper, and nitrogen. Nielson proposed a signaling function, perhaps via phosphoinositides, in animals.b... 

A lithium chloride solution caused changes in gravicur-vature, statocyte ultrastructure, and calcium balance in pea root, believed to be due to effects of lithium on the phosphoinositide second messenger system (678). The implications with regard to human parathyroid function are obscure. 

Facchinetti F., HackN. J., and Balazs R. (1998). Calcium influx via ionotropic glutamate receptors causes long lasting inhibition of metabotropic glutamate receptor-coupled phosphoinositide hydrolysis. Neurochem. Int. 33 263-270. 

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