Three additional inositol 1,4,5-trisphosphate receptors: molecular cloning and differential localization in brain and peripheral tissues.

Ross, Christopher A.; Danoff, Sonye K.; Schell, Michael J.; Snyder, Solomon H.; Ullrich, Axel

doi:10.1073/pnas.89.10.4265

Cited by 220 publications

(149 citation statements)

References 33 publications

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“…Type 1 InsP3R is the major neuronal type of InsP3R in the central nervous system, predominantly concentrated in cerebellar Purkinje cells, cerebral cortex, CA1 region of hippocampus, basal ganglia and thalamus (Mikoshiba, 1997;Ross et al, 1992). It is not surprising that an altered InsP3Rl functionality at the central nervous system level may be associated with pathological conditions.…”

Section: Discussionmentioning

confidence: 99%

An antidepressant behaviour in mice carrying a gene-specific InsP3R1, InsP3R2 and InsP3R3 protein knockdown

et al. 2008

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a b s t r a c tEvidence has accumulated for the involvement of Ca 2þ in the pathophysiology of mood disorders.Elevations in both resting and stimulated intracellular Ca 2þ levels in patients with affective disorders have been reported. The role of inositol-1,4,5-trisphosphate receptors (InsP3Rs), which allow mobilization of intracellular Ca 2þ stores, was, then, investigated in the mouse forced swimming test. InsP3Rantagonists (heparin, xestospongin C) as well as an inositol monophosphatase inhibitor (LiCl) showed an antidepressant activity of intensity comparable to clinically used antidepressants. InsP3Rl, InsP3R2 and InsP3R3 knockdown mice were obtained to investigate the role of InsP3R isoforms. We generated mice carrying a cerebral knockdown of InsP3Rl, InsP3R2 and InsP3R3 proteins by administering antisense oligonucleotides complementary to the sequence of InsP3Rl, InsP3R2 and InsP3R3. These antisensetreated mice showed a specific InsP3R protein level reduction in the mouse cerebral cortex and hippocampus, demonstrated by immunoblotting, immunoprecipitation and immunocytochemistry experiments. Knockdown mice for each InsP3R isoforms showed an antidepressant behaviour and the induced phenotype was reversible disappearing 7 days after the end of the treatment. The absence of impairment of locomotor activity and spontaneous mobility in InsP3R knockdown mice was revealed. These results indicate the involvement of the InsP3R-mediated pathway in the modulation of depressive conditions and may be useful for the development of new therapeutical strategies for the treatment of mood disorders.

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Section: Discussionmentioning

confidence: 99%

An antidepressant behaviour in mice carrying a gene-specific InsP3R1, InsP3R2 and InsP3R3 protein knockdown

et al. 2008

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“…Type 1 IP 3 R is the major neuronal type of IP 3 R in the CNS, which is predominantly concentrated in cerebellar Purkinje cells, cerebral cortex, the CA1 region of the hippocampus, basal ganglia and thalamus (Ross et al, 1992;Mikoshiba 1997). The role of IP 3 R1 at the CNS level was mainly investigated by means of IP 3 R1-deficient mice.…”

Section: Discussionmentioning

confidence: 99%

Knockdown of the type 2 and 3 inositol 1,4,5-trisphosphate receptors suppresses muscarinic antinociception in mice

et al. 2007

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Several literature reports indicate that supraspinal cholinergic antinociception induced both directly, through muscarinic agonists, and indirectly, by enhancing ACh extracellular levels through cholinesterase inhibitors, is mediated by M 1 receptor stimulation, indicating that M 1 muscarinic receptor subtype plays an essential role in the modulation of pain perception (Bartolini et al., 1992;Iwamoto and Marion, 1993;Ghelardini et al., 1996;Naguib and Yaksh, 1997;Ghelardini et al., 2000). More recently, intracellular mechanisms involved in supraspinal muscarinic antinociception in a condition of acute thermal nociception in normal animals have been investigated. M 1 muscarinic receptors typically couple via the ␣ subunits of the G q/11 family to activate phospholipase C (PLC) (Caulfield and Birdsall, 1998), and the activation of PLC results in hydrolysis of phosphatidyl 4,5-bisphosphate and production of inositol-1,4,5 trisphosphate (IP 3 ) and diacylglycerol (DAG). The main effect of DAG is to activate protein kinase C; IP 3 mediates the release of calcium from intracellular stores by binding to its receptors (Berridge, 1993). The involvement of receptor-mediated activation of the PLC-IP 3 pathway in the increase in pain threshold produced by administration of cholinomimetics was directly demonstrated. The inhibition of the IP 3 synthesis by pretreatment with LiCl, and the blockade of IP 3 receptors (IP 3 R) by administration of the IP 3 R antagonist heparin, dose dependently prevented physostigmine and oxotremorine antinociception (Galeotti et al., 2003).The receptor that recognizes IP 3 was first characterized as a protein called P400 that was enriched in normal cerebella (Mikoshiba et al., 1997); two other types of IP 3 receptors were then cloned. The original IP 3 receptor was named type 1 IP 3 receptor (IP 3 R1), whereas the others were named type 2 IP 3 receptor (IP 3 R2) and type 3 IP 3 receptor (IP 3 R3) (Patel et al., 1999). IP 3 Rs are recognized as a protein family of tetrameric ligand-gated Ca 2ϩ channels that allow mobilization of intracellular Ca 2ϩ stores in response to activation of cell surface receptors linked to IP 3 generation (Berridge, 1993). IP 3 R monomers are large proteins with a calculated molecular mass of about 300 kDa and all three isoforms of IP 3 R share 60 -70% amino acid similarity (Taylor et al., 1999).The aim of the present study was to investigate the role of type 1, 2 and 3 IP 3 Rs in the intracellular mechanism of muscarinic antinociception at a supraspinal level. To this purpose, we inhibited the expression of each IP 3 receptor subtype by using antisense oligonucleotides targeting IP 3 R mRNA sequences that are unique in the mouse genome and therefore assured stringent target selectivity.

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“…Three IP 3 R isoforms, designated IP 3 R1, IP 3 R2, and IP 3 R3, are encoded by distinct genes (6,37). IP 3 R isoform expression varies widely between different cell types.…”

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confidence: 99%

Type 1 inositol 1,4,5-trisphosphate receptors mediate UTP-induced cation currents, Ca²⁺ signals, and vasoconstriction in cerebral arteries

Zhao

Adebiyi²,

Blaskova

et al. 2008

American Journal of Physiology-Cell Physiology

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,4,5-trisphosphate receptors (IP3Rs) regulate diverse physiological functions, including contraction and proliferation. There are three IP3R isoforms, but their functional significance in arterial smooth muscle cells is unclear. Here, we investigated relative expression and physiological functions of IP3R isoforms in cerebral artery smooth muscle cells. We show that 2-aminoethoxydiphenyl borate and xestospongin C, membrane-permeant IP3R blockers, reduced Ca 2ϩ wave activation and global intracellular Ca 2ϩ ([Ca 2ϩ ]i) elevation stimulated by UTP, a phospholipase C-coupled purinergic receptor agonist. Quantitative PCR, Western blotting, and immunofluorescence indicated that all three IP3R isoforms were expressed in acutely isolated cerebral artery smooth muscle cells, with IP3R1 being the most abundant isoform at 82% of total IP3R message. IP3R1 knockdown with short hairpin RNA (shRNA) did not alter baseline Ca 2ϩ wave frequency and global [Ca 2ϩ ]i but abolished UTP-induced Ca 2ϩ wave activation and reduced the UTP-induced global [Ca 2ϩ ]i elevation by ϳ61%. Antibodies targeting IP3R1 and IP3R1 knockdown reduced UTP-induced nonselective cation current (Icat) activation. IP3R1 knockdown also reduced UTP-induced vasoconstriction in pressurized arteries with both intact and depleted sarcoplasmic reticulum (SR) Ca 2ϩ by ϳ45%. These data indicate that IP 3R1 is the predominant IP3R isoform expressed in rat cerebral artery smooth muscle cells. IP 3R1 stimulation contributes to UTP-induced I cat activation, Ca 2ϩ wave generation, global [Ca 2ϩ ]i elevation, and vasoconstriction. In addition, IP 3R1 activation constricts cerebral arteries in the absence of SR Ca 2ϩ release by stimulating plasma membrane Icat.cerebral artery smooth muscle cells; calcium wave; short hairpin RNA INOSITOL 1,4,5-trisphosphate (IP 3 ) receptors (IP 3 Rs) are expressed in many cell types and regulate several physiological functions, including development, muscle contraction, cell proliferation, and differentiation (1,45,47,56 Rs (7,43,54). IP 3 also activates cation channels in vascular smooth muscle cells through mechanisms that do not require the stimulation of sarcoplasmic reticulum (SR) Ca 2ϩ release (27, 54). In cerebral artery smooth muscle cells, IP 3 R activation stimulates TRPC3 channels, leading to Na ϩ influx, membrane depolarization, voltage-dependent Ca 2ϩ channel activation, and vasoconstriction (54). Thus IP 3 Rs regulate ion channel activity, Ca 2ϩ signals, and physiological functions in the vasculature. However, despite the functional importance of IP 3 Rs in arterial smooth muscle cells, specific IP 3 R isoforms that are expressed in this cell type and their functional significance are poorly understood.Three IP 3 R isoforms, designated IP 3 R1, IP 3 R2, and IP 3 R3, are encoded by distinct genes (6, 37). IP 3 R isoform expression varies widely between different cell types. Cerebellar Purkinje neurons express predominantly IP 3 R1, pancreatic ␤-cells primarily express IP 3 R3, and cardiac myocytes express IP 3 R2 (14, 48...

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Three additional inositol 1,4,5-trisphosphate receptors: molecular cloning and differential localization in brain and peripheral tissues.

Cited by 220 publications

References 33 publications

An antidepressant behaviour in mice carrying a gene-specific InsP3R1, InsP3R2 and InsP3R3 protein knockdown

An antidepressant behaviour in mice carrying a gene-specific InsP3R1, InsP3R2 and InsP3R3 protein knockdown

Knockdown of the type 2 and 3 inositol 1,4,5-trisphosphate receptors suppresses muscarinic antinociception in mice

Type 1 inositol 1,4,5-trisphosphate receptors mediate UTP-induced cation currents, Ca²⁺ signals, and vasoconstriction in cerebral arteries

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Three additional inositol 1,4,5-trisphosphate receptors: molecular cloning and differential localization in brain and peripheral tissues.

Cited by 220 publications

References 33 publications

An antidepressant behaviour in mice carrying a gene-specific InsP3R1, InsP3R2 and InsP3R3 protein knockdown

An antidepressant behaviour in mice carrying a gene-specific InsP3R1, InsP3R2 and InsP3R3 protein knockdown

Knockdown of the type 2 and 3 inositol 1,4,5-trisphosphate receptors suppresses muscarinic antinociception in mice

Type 1 inositol 1,4,5-trisphosphate receptors mediate UTP-induced cation currents, Ca2+ signals, and vasoconstriction in cerebral arteries

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Type 1 inositol 1,4,5-trisphosphate receptors mediate UTP-induced cation currents, Ca²⁺ signals, and vasoconstriction in cerebral arteries