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PubMed1994

Fc gamma receptor II stimulated formation of inositol phosphates in human platelets is blocked by tyrosine kinase inhibitors and associated with tyrosine phosphorylation of the receptor.

We report that activation of phospholipase C (PLC) by cross-linking of the platelet low-affinity Fc gamma receptor II (Fc gamma RII) is inhibited by two structurally distinct tyrosine kinase inhibitors, staurosporine and ST271. This contrasts with PLC activation induced by thrombin and U46619, a thromboxane mimetic, whose receptors have seven transmembrane domains characteristic of G-protein coupled receptors. Several proteins undergo phosphorylation on tyrosine on Fc gamma RII cross-linking upstream of protein kinase C (PKC), Ca2+ and aggregation, including the Fc gamma RII itself. The role of Fc gamma RII phosphorylation in the regulation of PLC is discussed.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1990

Leukotriene D4 induced calcium changes in U937 cells may utilize mechanisms additional to inositol phosphate production that are pertussis toxin insensitive but are blocked by phorbol myristate acetate.

DMSO differentiated U937 cells responded to 10(-6) M LTD4, LTB4 and FMLP with an increase in both InsP formation and [Ca2+]i. FMLP caused a greater rise in InsPs than either LTD4 or LTB4, which were equivalent. LTD4, however, caused a greater increase in [Ca2+]i than LTB4 (4-fold) or FMLP. The FMLP [Ca2+]i and InsP responses were abolished by pertussis toxin (100 ng/ml for 4 h) but were unaffected by PMA (10(-7) M for 3 min). In contrast, the LTD4 [Ca2+]i and InsP responses were reduced by only 50% by pertussis toxin, whilst PMA reduced the [Ca2+]i and InsP responses to LTD4 by 75 and 30%, respectively. These results suggest that mechanisms additional to InsP formation exist for mediating LTD4 evoked increases in [Ca2+]i.

Calcium↗
PubMed1993

Activation of human platelets by peroxovanadate is associated with tyrosine phosphorylation of phospholipase C gamma and formation of inositol phosphates.

Vanadate ions in the presence of H2O2 (peroxovanadate) induce a marked increase in the degree of tyrosine phosphorylation of proteins in human platelets. This increase preceded the onset of platelet shape change and aggregation, and is associated with activation of phospholipase C and increased [32P]phosphorylation of proteins of 47 kDa, a substrate for protein kinase C, and 20 kDa, a substrate for both myosin light-chain kinase and protein kinase C. The non-selective inhibitor of protein kinases, staurosporine, inhibits the increase in tyrosine phosphorylation of nearly all proteins and inhibits completely all other functional responses, suggesting that these events may be linked. In support of this, peroxovanadate stimulates tyrosine phosphorylation of phospholipase C gamma 1, suggesting that this may underlie its mechanism of platelet activation. Staurosporine also inhibited activation of phospholipase C by collagen, suggesting that tyrosine phosphorylation has an important role in the early stages of collagen-induced platelet activation.

Enzyme Activation↗
PubMed2003

Association of T cell antigen CD7 with type II phosphatidylinositol-4 kinase, a key component in pathways of inositol phosphate turnover.

CD7 is a 40-kDa glycoprotein that is expressed on prothymocytes and persists during T cell differentiation. CD7 has been demonstrated to generate, like other costimulatory molecules, intracellular signals that modulate T cell function. However, although it binds to phosphatidylinositol 3-kinase (PI 3-kinase), the signaling events mediated by CD7 are not completely understood. In this context, phosphatidylinositol 4-kinase (PI 4-kinase) is a key enzyme involved in a variety of events, from the modeling of the actin cytoskeleton to the activation of protein kinase C. In this study, we show for the first time that PI 4-kinase of 55 kDa can associate with CD7. The enzyme activity was insensitive to wortmannin, but was inhibited by adenosine, a characteristic for type II PI 4-kinase. Together, our findings demonstrate that type II PI 4-kinases are integral components of the CD7 signaling pathway and may play a role of CD7 in co-stimulation and thymic differentiation.

1-Phosphatidylinositol 4-Kinase↗
PubMed1986

Inositol phosphates turnover, cytosolic Ca++ and pH: putative signals for the control of cell growth.

The signals that induce a cell to divide are usually external and in the form of a binding of growth factors. We focussed our attention in defining the sequence of events which occurs after the binding of the mitogens to their surface receptors. One of the early membrane events stimulated by growth factors is a Na+ flux coupled to a H+ efflux that is typically inhibited by amiloride. The importance of this event and of the consequent cytoplasmic alkalinization for the cell proliferation is discussed. Recent data indicate that mitogens increase intracellular Ca++ levels and activate protein kinase C by inducing the hydrolysis of membrane phosphoinositides. A role for Ca++ and protein kinase C in activating Na+/H+ A role for Ca++ and protein kinase C in activating Na+/H+ exchange system is discussed. Finally a model is presented that illustrates the first membrane events stimulated by the growth factors. The model reveals an intimate interconnections between phosphoinositide metabolism, cytosolic Ca++ rise, protein kinase C and cytoplasmic alkalinization.

Amiloride↗
PubMed1997

Cross talk between T and B cells generates B antigen-presenting cells able to induce inositol phosphate production in T cells responding to Mls(a) superantigens.

Previous studies showed that activation of CD4+ T cells with mouse mammary tumor virus-encoded Mls(a) superantigens induces strong proliferative responses and interleukin-2 production but fails to elicit typical early T cell receptor (TCR)-mediated signal transduction events, such as hydrolysis of polyphosphoinositides (PI) or an increase in intracellular calcium. Here we show that the failure of Mls(a) antigen to activate PI hydrolysis applies when resting B cells are used as antigen-presenting cells (APC). By contrast, when Mls(a)-bearing B cells are activated for 24 h by exposure to lipopolysaccharide or, more importantly, to Mls(a)-reactive T cells or anti-CD40 antibodies the cells develop the capacity to elicit easily detectable PI turnover. These studies demonstrate that, for B cells as APC, the initiation of certain TCR-associated signal transduction pathways can depend on activation of the APC. The data suggest that cross talk between T cells and resting B cells can suffice to generate competent B APC and lead to the delayed initiation of signaling pathways important in T cell responses.

Animals↗
PubMed1995

Antinociceptive effect of alpha-trinositol, a novel D-myo-inositol phosphate derivative, in the formalin test in rats.

The antinociceptive effect of alpha-trinositol was examined in rats using the formalin test following systemic, spinal and local subcutaneous administration. Injection of formalin into the paw evoked two phases (phase 1: 0-9 min; phase 2: 10-60 min) of flinching behavior of the injected paw. Intrathecal administration of alpha-trinositol resulted in a dose-dependent suppression of the first (ED50: 8 microg) and second (ED50: 9 microg) phase of formalin-evoked behavioral response. Similarly, intraperitoneal delivery showed a dose-dependent reduction of the first (ED50: 83 mg/kg) and second (ED50: 56 mg/kg) phase of the formalin test. Subcutaneous injection of 100 microg, but not 10 mu g, alpha-trinositol into the rat paw together with the formalin solution, had no effect on the first phase, but reduced by 20% the second phase of behavior. These data show that alpha-trinositol produces a suppression of acute and prolonged nociceptive behaviors with a central mechanism of action, although some peripheral component may contribute to the reduction of the late phase following systemic administration.

Analgesia↗
PubMed1988

Activation of human neutrophils by substance P. Effect on oxidative metabolism, exocytosis, cytosolic Ca2+ concentration and inositol phosphate formation.

The neuropeptide substance P (SP), which has been suggested to mediate neurogenic inflammation, induces in human neutrophils the activation of the respiratory burst measured as O2 consumption and H2O2 production, and a cytochalasin B-dependent secretion of specific and azurophilic granules. The SP(4-11) fragment is much more stimulant than the entire molecule, whereas the SP(1-4) fragment is inactive. The respiratory and secretory response to SP are associated with an activation of phosphoinositide turnover, of Ca2+ influx and release from intracellular stores. Pertussis toxin inhibits 70% of the respiratory response and the residual 30% activity remains, even increasing 10-fold the concentration of the toxin. 1-(5-Isoquinolinesulfonyl)-2-methylpiperazine, a putative inhibitor of protein kinase C, does not modify the respiratory response to SP. Cytochalasin B significantly depresses the activation of the respiration by SP, whereas it moderately enhances the activation of phosphoinositide turnover and potentiates the increase of intracellular Ca2+ concentration. The results are discussed in relation to the receptor apparatus involved in SP activity, the signal transduction sequence activated by SP for the stimulation of NADPH oxidase, and the role of cell response to SP in the inflammatory process.

Calcium↗
PubMed2002

Scale-up potential of ion-pair high-performance liquid chromatography method to produce biologically active inositol phosphates.

This study was undertaken to evaluate the possibility that an analytical ion-pair HPLC procedure used to determine phytic acid (IP6) and its degradation products (IP3-IP5) can be transformed to a preparative purification method. A commercial phytic acid (CPA) preparation was separated into its component fractions of IP3, IP4, IPS, and IP6 on two C18 columns (1.8 and 4.2 ml) using 51% methanol containing 0.6-1% tetrabutylammonium hydroxide as ion-pair reagent and 0-0.025 M formic acid (pH 4.3) as eluent at 1.7 and 3.0 cm/min linear velocity, respectively, and 40 degrees C. Elution was monitored at 40 degrees C by a refractive index detector. Reproducible separation of CPA into four well-resolved peaks on these columns was possible after optimizing method variables, particularly the concentration of ion-pair reagent in the injected sample (>1.5%). The same separations were obtained after CPA loads were scaled up 25 times on a steel column (15 cm x 19 mm I.D.), packed with Ethyl C2 sorbent (10 microm) and on a 25 cm x 21.2 mm I.D. C18 column, but at a reduced linear velocity to increase the resolution. Therefore, this optimization of separation not only is useful for analysis of phytic acid and its degradation products but also it provides key parameters for scale up for further fractionation and characterization.

Chromatography, High Pressure Liquid↗
PubMed1992

In vivo efficacy of a novel inhibitor of selected signal transduction pathways including calcium, arachidonate, and inositol phosphates.

Aberrant signal transduction has been implicated in malignant transformation, growth, and progression. This has led to the proposal to use inhibitors of signal transduction pathways to treat cancer. One approach to circumventing potential toxicity and improving efficacy would be to target pathways upon which cancer cells selectively depend. Pathways associated with the malignant process involve calcium fluxes, the release of arachidonic acid, and the generation of phosphoinositides. In this report, CAI (L651582, NSC 609974), a substituted carboxyamido-imidazole and novel inhibitor of these selected signal transduction pathways, inhibits anchorage-dependent and -independent growth in a large series of human cancer cell lines. CAI pretreatment of HT-29 human colon cancer and 5R ras-transfected rat embryo fibroblast cells inhibits the formation and growth of experimental pulmonary metastases in nude mice. Oral administration of CAI in PEG-400 vehicle arrests growth and metastasis of transplanted human melanoma and ovarian cancer xenografts. No significant gross or histological toxicity was observed at CAI doses yielding blood levels in the concentration range demonstrated to inhibit select signal transduction pathways in vitro. These data indicate the feasibility and demonstrate a potential selectivity and sensitivity of using specific signal transduction inhibitors for the experimental treatment of cancer.

Aminoimidazole Carboxamide↗
PubMed1996

Effect of anoxia on cyclic nucleotides and inositol phosphate turnover in cardiac myocytes.

The loss of 5'-nucleotides (especially ATP and GTP) from cardiac muscle cells is a distinguishing feature of myocardial ischemia. Isolated adult rat cardiac myocytes were used as a model system to determine whether GTP depletion could affect (1) the ability of the myocytes to synthesize cyclic GMP (cGMP), or (2) the ability of the myocytes to respond to alpha-adrenergic challenge. Myocytes were made anoxic for 30- or 60-min periods, then challenged with either 1 mM sodium nitroprusside (NaNP) for 1 min or 40 microM norepinephrine (NE) for 20 min. The cells were extracted and the extracts assayed for cyclic GMP (NaNP challenge) or phosphoinositides (NE challenge). When challenged with NaNP, anoxic myocytes made up to five-fold more cGMP than aerobic controls (1401 +/- 353 fmol cGMP/mg cell protein in anoxic cells v 121 +/- 23 fmol/mg in aerobic controls). Phosphoinositide turnover was reduced in anoxic cells v aerobic controls. Stimulation of this pathway by NE was reduced two-fold after 30 min of anoxia, and abolished after 60 min of anoxia. Similar results were obtained with 30 microM and 60 microM phenylephrine. The authors concluded that nucleotide depletion under anoxic conditions has no effect on the production of cyclic GMP, but may interfere with the linkage of alpha-adrenergic receptors to phosphatidylinositol breakdown.

Animals↗
PubMed1991

M3-subtype muscarinic receptor that controls intracellular calcium release and inositol phosphate accumulation in gastric parietal cells.

The muscarinic receptor subtype which triggers acid secretion was investigated in isolated rabbit gastric parietal cells. Cytosolic free Ca2+ concentration ([Ca2+]i), measured with the fluorescent indicator FURA-2, increased rapidly after full agonist (carbachol) stimulation (6-8 sec), then returned to an intermediate sustained value. Other M2-agonists, oxotremorine and arecoline, produced a partial [Ca2+]i increase, whereas M1-agonists, pilocarpine and [4-m-chlorophenylcarbamoyloxyl]-2-butynyl-trimethylammonium, were without any significant effect. [Ca2+]i rise was inhibited by selective muscarinic antagonists: atropine greater than 4-diphenylacetoxy-N-methyl-piperidine methbromide greater than quinuclidinylbenzilate (QNB) greater than pirenzepine greater than 11-[[2-[(diethylamino)methyl]-1-piperidinyl]acetyl]-5,11-dihydro-6H- pyrido[2,3-b][1,4]benzodiazepine-6-one, this sequence being characteristic of the involvement of an M3-subtype. This inhibition was shown to be stereoselective; dexetimide and (-)QNB were more potent than levetimide and (+)QNB. The IC50 values for inhibition of [Ca2+]i increase by muscarinic antagonists were in good agreement with those obtained for inhibition of phospholipase C activation. In conclusion, the muscarinic receptor that controls acid secretion appears to be of the M3-subtype and the biochemical events coupled to the activation of this receptor system are also controlled through the same subtype.

Acetylcholine↗
PubMed1998

Atrial natriuretic factor-induced amylase output in the rat parotid gland appears to be mediated by the inositol phosphate pathway.

In previous in vivo studies we have reported that atrial natriuretic factor enhanced induced salivary secretion and increased isoproterenol-induced amylase release in the rat suggesting that, ANF effect could be mediated by phosphatidylinositol hydrolysis. In the present work, the effect of ANF on rat parotid tissue incubated in vitro was investigated with the aim to assess whether the phosphoinositol pathway was involved in ANF intracellular signaling in the parotid gland. Results showed that ANF induced a dose dependent increase in amylase fractional release, which was lower than that evoked by any concentration of isoproterenol. Furthermore 100 nM ANF enhanced isoproterenol-evoked amylase release. The effect of ANF was not affected in the presence of propranolol suggesting the noninvolvement of the beta adrenergic receptor, which is the main stimulus for the output of the enzyme in the parotid gland. However, ANF increased phosphatidylinositol hydrolysis, which implies an increase in intracellular calcium, which is necessary for the achievement of maximal response in amylase release. This effect was abolished in the presence of neomycin supporting ANF direct stimulation of phospholipase C. These results suggest the involvement of the C type natriuretic peptide receptor coupled to phospholipase C in ANF evoked amylase release and ANF enhancement of the isoproterenol-induced output of the enzyme.

Adrenergic beta-Agonists↗
PubMed1989

Pyrethroids: involvement of sodium channels in effects on inositol phosphate formation in guinea pig synaptoneurosomes.

The effects of pyrethroids were studied on phosphoinositide breakdown in guinea pig synaptoneurosomes. Similar to other agents that activate voltage-dependent sodium channels, type I and type II pyrethroids stimulated phosphoinositide breakdown. Type II pyrethroids, like deltamethrin and fenvalerate, were more potent and, at least for deltamethrin, more efficacious than type I pyrethroids, like allethrin, resmethrin and permethrin. The effects of type II pyrethroids could be partially inhibited by the sodium channel blocker tetrodotoxin. The effects of allethrin and resmethrin were not affected by 5 microM tetrodotoxin. Stimulation of phosphoinositide breakdown by fenvalerate was additive to the stimulation elicited by the receptor agonists carbamylcholine and norepinephrine, but not to the stimulation elicited by sodium channel agents (batrachotoxin, scorpion venom and pumiliotoxin B). Stimulation by allethrin was not additive to the stimulation elicited either by receptor agonists or sodium channel agents. A submaximal concentration of allethrin, a type I pyrethroid, did not greatly affect the dose-dependent stimulation elicited by a type II pyrethroid, deltamethrin, while a higher concentration of allethrin prevented further stimulation by type II pyrethroids. A local anesthetic, dibucaine, which inhibits sodium channel activation, inhibited phosphoinositide breakdown induced by type II, but not by type I pyrethroids, except at higher concentrations. Thus, type II pyrethroids appear to stimulate phosphoinositide breakdown in synaptoneurosomes in a manner analogous to other sodium channel agents, while type I pyrethroids elicit phosphoinositide breakdown by a different mechanism, probably not involving sodium channels.

Animals↗
PubMed1991

Mastoparan, a novel mitogen for Swiss 3T3 cells, stimulates pertussis toxin-sensitive arachidonic acid release without inositol phosphate accumulation.

Mastoparan, a basic tetradecapeptide isolated from wasp venom, is a novel mitogen for Swiss 3T3 cells. This peptide induced DNA synthesis in synergy with insulin in a concentration-dependent manner; half-maximum and maximum responses were achieved at 14 and 17 microM, respectively. Mastoparan also stimulated DNA synthesis in the presence of other growth promoting factors including bombesin, insulin-like growth factor-1, and platelet-derived growth factor. The synergistic mitogenic stimulation by mastoparan can be dissociated from activation of phospholipase C. Mastoparan did not stimulate phosphoinositide breakdown, Ca2+ mobilization or protein kinase C-mediated phosphorylation of a major cellular substrate or transmodulation of the epidermal growth factor receptor. In contrast, mastoparan stimulated arachidonic acid release, prostaglandin E2 production, and enhanced cAMP accumulation in the presence of forskolin. These responses were inhibited by prior treatment with pertussis toxin. Hence, mastoparan stimulates arachidonic acid release via a pertussis toxin-sensitive G protein in Swiss 3T3 cells. Arachidonic acid, like mastoparan, stimulated DNA synthesis in the presence of insulin. The ability of mastoparan to stimulate mitogenesis was reduced by pertussis toxin treatment. These results demonstrate, for the first time, that mastoparan stimulates reinitiation of DNA synthesis in Swiss 3T3 cells and indicate that this peptide may be a useful probe to elucidate signal transduction mechanisms in mitogenesis.

1-Methyl-3-isobutylxanthine↗
PubMed1991

The bradykinin receptor--a putative receptor-operated channel in PC12 cells: studies of neurotransmitter release and inositol phosphate accumulation.

Bradykinin (BK) induced [3H]norepinephrine [( 3H]NE) release and phosphatidylinositol turnover were investigated in PC12 cells. Induction of [3H]NE release by BK is mediated by activation of BK-B2-receptors, as determined using type specific BK receptor antagonists. BK induces [3H]NE release with a half maximal effective concentration of 30 +/- 0.5 nM, and reaches maximal net fractional release of 9.0 +/- 1% with 200 nM BK. The BK-induced release is Ca2+ dependent, reaching maximal release at 1.0 mM Ca2+, is pertussis toxin insensitive (1 microgram/ml), slightly increased by a dibutyryl cAMP (1 mM) and not affected by inhibitors of the cyclooxygenase or lipoxygenase pathways. Voltage-sensitive Ca2+ channel blockers, verapamil (10 microM), nifedipine (10 microM), and omega-conotoxin (CgTx 10 nM), do not block the BK-induced release. However, a considerable inhibitory effect was obtained by divalent cations Co2+ (ED50 = 0.2 mM) and Ni2+ (ED50(2)+ = 1 mM). These results indicate the involvement of a Ca2+ channel in the BK-mediated release which is different from the L- or N-type voltage sensitive calcium channels. Whereas [Ca2+]ex is essential for the BK-induction of catecholamine release, the rise in level of InsP's induced by BK in the presence or in the absence of [Ca2+]ex is similar up to concentration of 1 microM. This indicates that the rise in InsP's induced by BK is not sufficient to cause neurotransmitter release. Moreover, subsequent addition of Ca2+ to BK-stimulated cells in Ca(2+)-free medium yields no release. Hence, no activity triggered by BK alone could be further stimulated by Ca2+ for induction of release.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Gland Neoplasms↗
PubMed1997

FP prostaglandin receptors mediating inositol phosphates generation and calcium mobilization in Swiss 3T3 cells: a pharmacological study.

A detailed pharmacological characterization of the prostaglandin (PG) receptor coupled to phosphoinositide (PI) turnover and intracellular calcium mobilization in Swiss 3T3 mouse fibroblast cells was undertaken. The pharmacological profile of this functional receptor was compared with the pharmacological profile of specific [3H]PGF2 alpha binding to bovine corpus luteum membranes, which are known to contain a bona fide FP receptor. PGs that were potent stimulators and full agonists in the PI turnover assay in the 3T3 cells were the following (for all, n = 3-45): 16-phenoxy-PGF2 alpha (EC50 = 0.61 +/- 0.1 nM), cloprostenol (EC50 = 0.73 +/- 0.04 nM), 17-phenyl-PGF2 alpha (EC50 = 2.71 +/- 0.35 nM), fluprostenol (EC50 = 3.67 +/- 0.61 nM), PhXA85 (EC50 = 27.3 +/- 5.63 nM) and PGF2 alpha (EC50 = 28.5 +/- 5.26 nM). However, PGD2 (EC50 = 155 +/- 29.9 nM; Emax = 49% of cloprostenol), PGE2 (EC50 = 2570 +/- 566 nM; Emax = 59%) and U46619 (EC50 = 1060 +/- 310 nM; Emax = 63%) were less potent and were partial agonists, and iloprost and BW245C were inactive. Although the PGs tested exhibited lower affinities in the 3[H]PGF2 alpha binding assay than their functional potencies in the PI turnover assay, the rank orders of potencies and affinities were well correlated (r = 0.94; n = 15 compounds). However, the PI turnover assay was more sensitive than the calcium mobilization assay for rank ordering PG agonists. In conclusion, the Swiss 3T3 cells express an FP receptor coupled to PI turnover and intracellular Ca+2 mobilization signal transduction pathways. The pharmacological profile of this receptor was similar to that of the FP receptor found in the bovine corpus luteum, a tissue previously used to clone the first pharmacologically defined FP receptor.

3T3 Cells↗
PubMed2001

alpha(1)-adrenergic stimulation mediates Ca(2+)-dependent inositol phosphate formation through the alpha(1B)-like adrenoceptor subtype in adult rat cardiac myocytes.

We studied the effects of increased Ca(2+) influx on alpha(1)-adrenoceptor-stimulated InsP formation in adult rat cardiac myocytes. We further examined if such effects could be mediated through a specific alpha(1)-adrenoceptor subtype. [(3)H]InsP responses to adrenaline were dependent on extracellular Ca(2+) concentration, from 0.1 microM to 2 mM, and were completely blocked by Ca(2+) removal. However, in cardiac myocytes preloaded with BAPTA, a highly selective calcium chelating agent, Ca(2+) concentrations higher than 1 microM had no effect on adrenaline-stimulated [(3)H]InsP formation. Taken together these results suggest that [(3)H]InsP formation induced by alpha(1)-adrenergic stimulation is in part mediated by increased Ca(2+) influx. Consistent with this, ionomycin, a calcium ionophore, stimulated [(3)H]InsP formation. This response was additive with the response to adrenaline stimulation implying that different signaling mechanisms may be involved. In cardiac myocytes treated with the alpha(1B)-adrenoceptor alkylating agent, CEC, [(3)H]InsP formation remained unaffected by increased Ca(2+) concentrations, a pattern similar to that observed when intracellular Ca(2+) was chelated with BAPTA. In contrast, addition of the alpha(1A)-subtype antagonist, 5'-methyl urapidil, did not affect the Ca(2+) dependence of [(3)H]InsP formation. Neither nifedipine, a voltage-dependent Ca(2+) channel blocker nor the inorganic Ca(2+) channel blockers, Ni(2+) and Co(2+), had any effect on adrenaline stimulated [(3)H]InsP, at concentrations that inhibit Ca(2+) channels. The results suggest that in adult rat cardiac myocytes, in addition to G protein-mediated response, alpha(1)-adrenergic-stimulated [(3)H]InsP formation is activated by increased Ca(2+) influx mediated by the alpha(1B)-subtype.

Adrenergic Antagonists↗