Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

By employing early-passaged rabbit kidney epithelial cells in tissue culture, we demonstrated that angiotensin II (AII) has unique mechanisms of signal transduction. First, unlike its action in other target tissues, micromolar concentrations of AII are required to induce small rises in cytosolic calcium, [Ca2+]i, an action which is not accompanied by the release of inositol phosphates (IP). In contrast, nanomolar bradykinin (BK) mobilizes [Ca2+]i through activation of phospholipase C and release of IP. Neither of these stimulated calcium responses exhibits pertussis toxin (PTx) sensitivity. Secondly, AII and BK at 10(-9) to 10(-7) M stimulate cAMP indirectly through PGE2 production in distal cells. AII- and BK-stimulated PGE2 release is PTx inhibitible, suggestive of the presence of a GTP binding protein mediating the response. By contrast, arginine vasopressin fails to elicit rises in [Ca2+]i but exerts its primary effect on cAMP production in distal cells via direct coupling to a stimulatory GTP binding protein, as evidenced by uncoupling with cholera toxin. Regulation of PGE2 synthesis appears to occur via phospholipase A2, not C, by all three peptides.
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PMID:Relationship between phospholipase C activation and prostaglandin E2 and cyclic adenosine monophosphate production in rabbit tubular epithelial cells. Effects of angiotensin, bradykinin, and arginine vasopressin. 244 59

In primary culture of anterior pituitary cells, BAY-K-8644, a calcium channel agonist, stimulated PRL secretion by 83% with EC50 of 18 nM. This effect was blocked by nifedipine, a calcium channel antagonist. The stimulations of PRL secretion induced by potassium (50 mM) and BAY-K-8644 were additive. Dopamine inhibited basal as well as BAY-K-8644-stimulated PRL secretion by 64% and 75%, respectively, and with respective EC50 values of 4.5 and 0.6 nM. In the presence of 50 mM K+, dopamine only partially blocks the dose-dependent stimulation of PRL secretion induced by the calcium channel agonist. The inhibitory dopamine effect was blocked by (+)butaclamol, a specific dopamine receptor antagonist. The dopamine response was also blocked by 1-sulpiride, a specific dopamine D2 receptor antagonist, and mimicked by RU 24926, a specific dopamine D2 receptor agonist, suggesting that the dopamine effect on BAY-K-8644-stimulated PRL secretion was mediated through a D2 dopamine receptor. Although unknown, the mechanism by which dopamine inhibited the BAY-K-8644-stimulated PRL secretion involves a GTP binding protein sensitive to Bordetella pertussis toxin. In fact, the dopamine inhibition of PRL secretion induced by the calcium channel agonist was blocked by the pretreatment of cells with the toxin. These results suggest that dopamine D2 receptors in lactotroph cells modulate calcium influx through a GTP binding protein.
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PMID:Dopamine inhibits prolactin secretion stimulated by the calcium channel agonist Bay-K-8644 through a pertussis toxin-sensitive G protein in anterior pituitary cells. 245 6

We investigated the mechanism for lithium-induced inhibition of vasopressin-stimulated adensoine 3',5'-cyclic monophosphate (cAMP) production in the renal epithelial cell line LLC-PK1. In LLC-PK1 membranes lithium caused direct inhibition of hormone-stimulated adenylate cyclase activity by competing with magnesium. Fifty percent inhibition occurred at 20 mM lithium. The maximum transport activity (Vmax) but not the activation constant (Ka) for activation by vasopressin was altered. Activation by GTP and its nonhydrolyzable analogues was also inhibited by lithium. Furthermore, kinetic studies revealed that the lag phase in the activation of adenylate cyclase by 5'-guanylimi-dotriphosphate [Gpp(NH)p] was prolonged from 1 to 3 min, suggesting an effect of lithium on magnesium-dependent activation of the stimulatory GTP binding protein Gs. The function of the corresponding inhibitory GTP-binding protein Gi, as assessed by GTP inhibition of vasopressin-stimulated adenylate cyclase activity in the presence and absence of pertussis toxin pretreatment, was unaffected. Intact LLC-PK1 cells incubated in 10 mM lithium (approximate urinary concentration in lithium-treated patients) attained an intracellular lithium concentration of 17 mM, which led to a 40% reduction in cAMP formation. Magnesium loading of intact cells with the ionophore A23187 reversed the inhibitory effect of lithium. It is concluded that lithium directly inhibits the activation of vasopressin-sensitive adenylate cyclase in renal epithelia by competing with magnesium for activation of Gs. This direct effect on Gs activation accounts for the inhibitory effect of lithium on cAMP production in the intact cell.
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PMID:Mechanism of Li inhibition of vasopressin-sensitive adenylate cyclase in cultured renal epithelial cells. 246 Oct 98

The effect of neuropeptide Y (NPY) on cytosolic free Ca2+ concentration ([Ca2+]i) was studied in cultured smooth muscle cells from porcine aorta (PASMC) and compared with the effect of bradykinin (BK) and angiotensin II (ATII) on [Ca2+]i. All peptides induced dose-dependent and transient rises in [Ca2+]i which were not blocked by extracellular EGTA, but the NPY response was different from the others' as follows. First, the [Ca2+]i rise induced by NPY was not as rapid as that induced by BK or ATII. Second, pertussis toxin abolished the [Ca2+]i rise induced by NPY, but not by BK or ATII. Third, following initial treatment with BK, PASMC were able to respond to NPY, but not to ATII. Finally, BK and ATII, but not NPY, significantly increased inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) generation. Although NPY attenuated forskolin-induced accumulation of cyclic AMP, forskolin- and 3-isobutyl-1-methyl-xanthine-induced alterations in intracellular cyclic AMP did not affect the NPY-induced [Ca2+]i rise. These results suggest that NPY increases [Ca2+]i by a pertussis toxin-sensitive GTP binding protein-involved mechanism which is not mediated by the intracellular messengers such as Ins(1,4,5)P3 and cyclic AMP.
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PMID:Neuropeptide Y-induced intracellular Ca2+ increases in vascular smooth muscle cells. 248 Sep 20

Carbachol, histamine and bradykinin activate phospholipase C in pertussis toxin-insensitive manner in human astrocytoma cells. Pretreatments of the cells with these agonists resulted in the reduction of GTP gamma S-induced accumulation of inositol phosphates in membrane preparations. Treatment of cells with carbachol mobilized GTP gamma S binding activities as well as muscarinic receptors from heavy membrane fraction to light fraction, reflecting from an agonist-induced desensitization. The treatment of the cells with agonists reduced a 32 kDa GTP binding protein in heavy membrane fraction, determined by a photoaffinity labeling with [35S]GTP gamma S. The data suggest that the 32 kDa GTP binding protein is involved in desensitization by agonists which activate phospholipase C in human astrocytoma cells.
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PMID:GTP gamma S binding activities were reduced in heavy membrane fraction during desensitization by Ca-mobilizing agonists in human astrocytoma cells. 250 Jun 83

The properties of thromboxane A2 (TXA2) receptors were examined in 1321N1 human astrocytoma cells. 9,11-Epithio-11,12-methanothromboxane A2 (STA2), a stable analogue of TXA2, stimulated the accumulation of inositol phosphates (IPs) with an EC50 of about 50 nM. The STA2-induced accumulation of IPs was inhibited concentration dependently by ONO3708, a TXA2 receptor antagonist, with an inhibition constant (Ki) of about 10 nM. Inositol trisphosphate (IP3) was accumulated more rapidly than inositol bisphosphate (IP2) in response to STA2. HPLC analysis indicated that inositol 1,4,5-trisphosphate accumulated in the presence of STA2. STA2 alone had no effect on the accumulation of IPs in membrane preparations but it potentiated the accumulation induced by GTP gamma S. [3H]SQ29548, a TXA2 receptor antagonist, bound specifically to TXA2 receptors, expressing a single binding site with a dissociation constant (Kd) of 10.9 nM. The competition curve for STA2 inhibition of [3H]SQ29548 binding was shifted to the right and was steeper in the presence of GTP gamma S. Pertussis toxin (IAP) elicited ADP-ribosylation of 41KD protein but had no effect on the sensitivity to GTP of the STA2 inhibition of SQ29548 binding or of STA2-induced accumulation of IPs. It is concluded from these results that the stimulation of TXA2 receptors results in activation of phospholipase C via a GTP binding protein and that the protein is not a substrate for IAP.
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PMID:Thromboxane A2 activates phospholipase C in astrocytoma cells via pertussis toxin-insensitive G-protein. 254 56

A mu-opioid receptor-GTP binding protein (mu-opioid receptor-G-protein) complex from the 7315c cell was solubilized with CHAPS (3-[(3-cholamidopropyl)dimethylammonio]-1-propane sulfonate) and reconstituted into phospholipid vesicles. Pretreatment of the tissue with either [3H]etorphine or morphine greatly improved recovery of the receptor and maintained it in a GTP-sensitive state. GTP sensitivity was consistent with the hypothesis that a receptor-G-protein complex had been obtained. Other evidence consistent with this hypothesis was that recovery of the solubilized, prelabelled receptor was decreased by approximately 70% by pretreatment of 7315c cells with pertussis toxin. The reconstituted receptor was mu-selective: DAGO (Tyr-D-Ala-Gly-Met-Phe- NH(CH2)2OH), but not ICI 174864 or U50488-H, displaced [3H]etorphine binding with high affinity. The affinity of the reconstituted receptor for [3H]etorphine (1.25 +/- 0.20 nM) was similar to that observed for the membrane-associated receptor (0.53 +/- 0.25 nM). GTP gamma S decreased this affinity 3-fold without changing the number of binding sites. The potencies of GTP gamma S and GTP in diminishing [3H]etorphine binding were similar in the membrane and vesicle preparations, but were 10-fold lower than the potencies observed in diminishing binding to the solubilized receptor. The ability to reconstitute a functional mu-opioid receptor-G-protein complex will facilitate further study of the structure and function of the receptor and the specific identification of the associated GTP-binding protein(s).
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PMID:Reconstitution of the solubilized mu-opioid receptor coupled to a GTP-binding protein. 255 7

The relationship between prostaglandin E2 (PGE2) receptor and GTP binding protein was studied in the normal and aminonucleoside-induced nephrotic rats. Affinities and maximal binding sites of PGE2 receptors in renal medulla of the male Wistar rats were examined by Scatchard analysis. Cyclic AMP and inositol phosphates were measured in the medulla tissues to examine the intracellular mediators of PGE2 receptor activation. The following results were obtained: 1) GTP gamma S, a nonhydrolyzable guanine nucleotide, increased the 3H-PGE2 binding in a concentration-dependent manner, and pertussis toxin partially attenuated the GTP gamma S effect, 2) PGE2 stimulated the accumulation of inositol phosphates in the medullary tissues with a similar dissociation constant (Kd) value of binding analysis, and high concentrations of PGE2 stimulated the accumulation of cyclic AMP, 3) the affinity of PGE2 receptors in the renal cellular membranes taken from nephrotic rats were significantly lower than that in normal rats, and the effects of GTP gamma S on the affinity was greater in nephrotic rat kidney than normal one. These results suggest that PGE2 receptor of the rat kidney links to a GTP binding protein. In nephrotic rat kidney, damages occur not only in PGE2 receptor but also in the GTP binding protein.
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PMID:[Prostaglandin E2 receptor and GTP binding protein in the normal and nephrotic rat kidney]. 255 13

Acetylcholine (Ach) was tested for its effect on calcium currents in primary cultures of embryonic rat hippocampal neurons. Ach reversibly depressed, in a dose-dependent way, the high voltage activated (HVA) Ca currents. The effect was antagonized by atropine. Our results suggest that a pertussis toxin (PTX)-sensitive GTP binding protein (G-protein) is involved in the signal transduction mechanism between the Ach receptor and the HVA Ca channel. Activating rather than depressive effects of Ach were observed on the low voltage-activated component of Ca currents. This effect was also antagonized by atropine but is not mediated by a PTX-sensitive G-protein.
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PMID:Opposing effects of acetylcholine on the two classes of voltage-dependent calcium channels in hippocampal neurons. 255 10

The neurotransmitters histamine, dopamine and the peptide Phe-Met-Arg-Phe-NH2 (FMRFa) cause presynaptic inhibition in the nervous system of the marine mollusk Aplysia Californica by combined down-modulation of a Ca++ conductance and up-modulation of a K+ conductance. The action of FMRFa on the S-type K+ channels of Aplysia sensory neurons is mediated by a metabolite of the 12-lipoxygenase pathway of arachidonic acid, possibly 12-HPETE. A Pertussis toxin-sensitive GTP binding protein couples FMRFa receptor to the activation of the arachidonic cascade. Once produced, 12-HPETE does not require ATP- or GTP-dependent processes to act on the K+ channels, but it may directly modulate the channel via an external membrane receptor. Based on this observation, a role for eicosanoids as possible intercellular messengers in the C.N.S. is discussed.
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PMID:Arachidonic acid metabolites as mediators of synaptic modulation. 256 69


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