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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To characterize the excitatory purinoceptors in vascular smooth muscle cells and the biochemical mechanisms of their actions, the effects of ATP and other nucleotides on Ca2+ mobilization in cultured smooth muscle cells mainly from rat aorta were investigated. ATP induced a transient and dose-dependent increase in the cytosolic Ca2+ concentration. ATP also induced a rapid production of inositol trisphosphate (IP3). The agonist form of ATP was metal-free ATP and its half-maximal effect was obtained at about 0.1 microM. 4-beta-Phorbol 12-myristate 13-acetate (PMA) or 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate (TMB-8) inhibited both Ca2+ response and IP3 production. In addition, TMB-8 but not PMA, significantly decreased the amount of releasable Ca2+ presumably in the sarcoplasmic reticulum. Pertussis toxin also inhibited the Ca2+ response. Based on the dose-dependent effects of various nucleotides and adenosine on the Ca2+ response, it was concluded that the P2 subclass of purinoceptor is involved in the observed ATP effects. In addition, the observed absence or very weak effect of alpha, beta-methylene ATP relative to the effect of ATP suggests that the excitatory P2-purinoceptors in vascular smooth muscle cells do not form a homogeneous group, because the opposite order of potency for these two nucleotides was reported previously for the P2 purinoceptors involved in contraction of some isolated blood vessels.
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PMID:ATP-induced calcium transient in cultured rat aortic smooth muscle cells. 350 44

Hormonal inhibition of adenylate cyclase is mediated by inhibitory receptors and a guanyl nucleotide-binding coupling protein, termed Gi. Similarly, transducin (T), a guanyl nucleotide-binding protein, mediates activation of cGMP phosphodiesterase by the retinal photon receptor, rhodopsin. Gi and T are both heterotrimers consisting of alpha, beta, and gamma subunits; Gi alpha and G beta are similar to T alpha and T beta, respectively. T alpha hydrolyzes GTP in the presence of photolyzed, but not dark, rhodopsin and T beta gamma. Gi alpha and G beta gamma substituted for T alpha and T beta gamma to yield active hybrid complexes, T alpha G beta gamma and Gi alpha T beta gamma. In the absence of T components, rhodopsin-dependent GTPase activity of Gi alpha G beta gamma was observed. Pertussis toxin ADP-ribosylates both T alpha and Gi alpha; ADP-ribosylation of Gi alpha was negligible in the absence of G beta gamma. With G beta gamma, photolyzed, but not dark, rhodopsin unhibited ADP-ribosylation of Gi alpha. In the presence of G beta gamma and photolyzed rhodopsin, GDP and GDP beta S, but not Gpp(NH)p and GTP gamma S, increased the ADP-ribosylation of Gi alpha. The requirements for ADP-ribosylation of Gi alpha by pertussis toxin were similar to those for ADP-ribosylation of T alpha. Rhodopsin appears to interact with Gi in a manner similar to the inhibitory hormone receptors; photolyzed rhodopsin, the active species, corresponds to the agonist-occupied receptor, while dark rhodopsin, the inactive species, can be equated to the free receptor.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pertussis toxin-catalyzed ADP-ribosylation of adenylate cyclase. Effects of guanyl nucleotides and rhodopsin. 393 69

Hormonal inhibition of adenylate cyclase is mediated by a guanyl nucleotide binding protein, Gi, which is composed of alpha, beta, and gamma subunits (Gi alpha, G beta gamma). Pertussis toxin blocks hormonal inhibition by catalyzing the ADP-ribosylation of Gi alpha. With purified Gi subunits, but without nucleotides, it was observed that toxin-catalyzed ADP-ribosylation of Gi alpha was negligible in the absence of G beta gamma; ATP, previously shown to increase ADP-ribosylation in membranes, enhanced the ADP-ribosylation of Gi alpha in the absence, more than in the presence, of G beta gamma. Prior studies (Kanaho, Y., Tsai, S.-C., Adamik, R., Hewlett, E.L., Moss, J., and Vaughan, M. (1984) J. Biol. Chem. 259, 7378-7381) had demonstrated that rhodopsin, the retinal photon receptor protein, can replace inhibitory hormone receptors, and stimulate the hydrolysis of GTP by Gi alpha in the presence of G beta gamma. Photolyzed rhodopsin, but not the inactive, dark protein, inhibited ADP-ribosylation of Gi alpha in the presence of G beta gamma. ADP-ribosylation of Gi alpha, in the presence of G beta gamma and photolyzed (but not dark) rhodopsin was increased by guanosine 5'-O-(2-thiodiphosphate) or GDP, but not by (beta, gamma-methylene)guanosine triphosphate or guanosine 5'-O-(3-thiotriphosphate). Presumably, photolyzed rhodopsin and nucleoside triphosphate analogues activate Gi, whereas with dark rhodopsin and nucleoside diphosphates Gi is in the inactive state. The latter appears to be the preferred substrate for pertussis toxin. These observations are consistent with other evidence that rhodopsin and inhibitory hormone receptors are functionally similar.
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PMID:Effects of guanyl nucleotides and rhodopsin on ADP-ribosylation of the inhibitory GTP-binding component of adenylate cyclase by pertussis toxin. 643 19

ATP produced whole-cell potassium currents in cultured endothelial cells of the bovine brain cortical arteries. P2 purinoceptor agonists evoked similar currents with the order of their potency: 2-methylthio ATP > ATP >> alpha, beta-methylene ATP > or = UTP > or = ADP >> AMP. ATP-evoked currents were inhibited by GDP beta S, but not by pertussis toxin (PTX). Furthermore, a phospholipase C (PLC) inhibitor, protein kinase C inhibitor, or cAMP-dependent protein kinase inhibitor had no effect on the currents. In addition to these effects, ATP enhanced intracellular free Ca2+ concentration ([Ca2+]i) in the presence and absence of extracellular Ca2+, and this [Ca2+]i increase was not inhibited by a PLC inhibitor. These results, thus, provide an indication that ATP activates the potassium channel and enhances [Ca2+]i via a P2Y purinoceptor linked to a PTX-insensitive G-protein, which is not involved in a PLC-mediated signaling pathway.
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PMID:ATP activates the potassium channel and enhances cytosolic Ca2+ release via a P2Y purinoceptor linked to pertussis toxin-insensitive G-protein in brain artery endothelial cells. 748 26

Inhibition of insulin secretion by galanin is pertussis toxin (PTX) sensitive, suggesting the activation of one or more heterotrimeric (alpha, beta, gamma) G-proteins (Gi/Go). Multiple effectors, including the K+ATP and L-type Ca2+ channels, adenylyl cyclase, and an as yet unidentified system at a site close to exocytosis, are modulated by galanin. Therefore, it is necessary to delineate the particular G-proteins activated by the galanin receptor as a first step to understanding its net cellular response. During specific conditions, cholera toxin (CTX) can ADP-ribosylate the alpha i/alpha o-subunits of the PTX-sensitive substrates but only during receptor/G-protein interaction. Therefore, we used CTX-catalyzed ADP ribosylation to identify galanin receptor-associated G-protein alpha-subunits in RINm5F cells. Galanin enhanced the ADP ribosylation of membrane proteins separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) in two bands at 39,000 and 42,000 M(r). This labeling was blocked in membranes prepared from PTX-treated cells, enhanced by Mg2+, and showed a biphasic dependence on exogenous guanine nucleotides. Identification of the CTX ADP-ribosylated G-proteins by immunoprecipitation with selective antisera indicate activation by the galanin receptor of alpha i1 and alpha i3, which have the same mobility on SDS-PAGE (42,000 M(r)), and alpha i2 (39,000 M(r)). These studies provide evidence for the activation of multiple G-proteins by receptors for galanin in RINm5F cells.
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PMID:ADP ribosylation by cholera toxin identifies three G-proteins that are activated by the galanin receptor. Studies with RINm5F cell membranes. 750 45

In rat pituitary GH3 cells Ca2+ current through L-type channels is reduced by somatostatin. This modulation of channel activity by somatostatin receptors is mediated by a guanine nucleotide-binding regulatory protein (G protein). It is sensitive to pertussis toxin, indicating the involvement of a G(o)- or Gi-type G protein in this pathway. The identity of this G protein was determined by suppressing the expression of endogenous G proteins individually via intranuclear injection of antisense oligonucleotides. This method was applied to GH3 cells to screen several G protein alpha, beta and gamma subunits for their roles in the defined signal transduction pathway. The loss of somatostatin's modulating activity on the voltage-dependent Ca2+ channel after oligonucleotide injection revealed the involvement of G(o) alpha 2 beta 1 gamma 3 to the exclusion of other closely related subtypes.
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PMID:Somatostatin modulates voltage-dependent Ca2+ channels in GH3 cells via a specific G(o) splice variant. 758 46

A phospholipase-C-linked nucleotide receptor, sensitive to both uridine and adenosine triphosphate (UTP and ATP) has been cloned from NG108-15 neuroblastoma x glioma hybrid cells. We have tested whether activation of this receptor could inhibit the voltage-dependent K+ current [IK(M) or "M-current"] in NG108-15 cells recorded using whole-cell patch-clamp methods. Both UTP and ATP inhibited IK(M) by 44% and 42%, respectively, at 100 microM. Mean IC50 values were: UTP, 0.77 +/- 0.27 microM; ATP, 1.81 +/- 0.82 microM. The order of nucleotide and nucleoside activity at 100 microM was: UTP = ATP > ATP [gamma S] = ITP > 2-MeSATP > ADP = GTP >> AMP-CPP, adenosine, where ATP[gamma S] is adenosine 5'-O-(3-thiotriphosphate), ITP is inosine 5'-triphosphate, 2-MeSATP is 2-methylthio ATP and AMP-CPP is alpha, beta methylene ATP. This rank order accords with their activities at the cloned P2U receptor. Effects were not inhibited by suramin (up to 500 microM) or by pre-incubation for 12 h in 500 ng.ml-1 Pertussis toxin. Inhibition of IK(M) was frequently preceded by a transient outward current, probably a Ca(2+)-activated K+ current, responding to Ca2+ mobilization. No effect on the delayed rectifier K+ current was observed. These observations match those expected from stimulating other phospholipase-C-linked receptors in NG108-15 cells.
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PMID:Activation of nucleotide receptors inhibits M-type K current [IK(M)] in neuroblastoma x glioma hybrid cells. 789 8

The insulin secreting B cell is fitted with the two types of purinergic receptors: P2 (for ATP and/or ADP) and P1 (for adenosine). The activation of P2 purinoceptors by ATP or ADP evokes a biphasic stimulation of insulin secretion from isolated perfused rat pancreas; this stimulation is dose-dependent between 10(-6) and 10(-4) M. Non hydrolysable structural analogues are also effective, and the relative potency of various agonists (2-methylthio ATP >> ATP = ADP = alpha, beta-methylene ATP >> AMP) gave evidence for a P2y purinoceptor subtype. Proposed mechanisms include both an increased Ca2+ uptake and an increased intracellular Ca2+ mobilization via the hydrolysis of polyphosphoinositides. ATP (or ADP) potentiates physiological insulin-secreting agents (glucose and acetylcholine) and P2 purinoceptors could play a physiological role in the stimulation of insulin secretion. The activation of P1 purinoceptors (adenosine receptors) decreases insulin secretion. Using structural analogues of adenosine, the receptor was characterized as an A1 subtype; it is coupled to a pertussis toxin sensitive G protein and it inhibits adenylate cyclase. It is of physiological relevance that the B cell has the two types of purinoceptors with opposite effects. Recently, a metabolically stable structural analogue of ADP, adenosine-5'-0-(2-thiodiphosphate) or ADP beta S, has been described as a potent secretory agent, effective at nanomolar concentrations on isolated perfused rat pancreas. In vivo, this substance is able to increase insulin secretion and to improve glucose tolerance after IV administration in rats and oral administration in dogs. Furthermore in streptozotocin-induced diabetes. ADP beta S retains its insulin secreting effects. These results suggest that P2y purinoceptors could be a new target for antidiabetic drugs.
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PMID:Purinergic receptors on insulin-secreting cells. 802 Aug 70

In mammals, G-protein alpha, beta, gamma polypeptides are encoded by at least 16, 4 and 7 genes, respectively. G alpha-subunits bind and hydrolyze GTP and have the sites for bacterial toxin-catalyzed ADP-ribosylation. A structural model of G alpha-subunits can be defined on the basis of similarities between G alpha and other members of the GTP-binding proteins. The resulting G alpha model specifies the spatial relationship among the guanine nucleotide binding site, the binding site of the G beta gamma-subunit complex, likely regions of effector and receptor interaction, and sites of cholera or pertussis toxin-induced modification. The architecture of the G alpha core is the same as that of p21ras. Experimental evidence from immunological, molecular genetic and biochemical studies support the G alpha model. The G alpha-subunits alone were previously thought to act on the effector enzymes; However, recent evidence indicates that the G beta gamma-dimer also plays an important part in effector activation.
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PMID:[Structure and function of heterotrimeric G-proteins]. 803 66

In rabbit renal cortical collecting tubule (CCT), perfused in vitro at 38 degrees C, ATP in concentrations of 10(-7) M and greater inhibits arginine vasopressin (AVP)-stimulated osmotic water permeability (Pf). The P1-purinergic receptor antagonist 8-phenyltheophylline did not attenuate the inhibitory action of ATP, and the poorly hydrolyzable ATP analogue, 5'-adenylylimidodiphosphate (AMP-PNP), mimicked the effect of ATP, arguing against an effect of ATP on a P1 receptor or the "P site." Purinergic receptor agonists inhibited AVP-stimulated Pf with the following rank order efficacy: ATP = ADP = UTP = AMP-PNP = alpha, beta-methylene-ATP > 2-methylthio-ATP >> AMP > adenosine, consistent with the pharmacology of a "nucleotide" receptor subtype. Pertussis toxin pretreatment attenuated the action of 10(-5) and 10(-6) MATP; however, 10(-4) MATP failed to inhibit the hydrosmotic action of forskolin or 8-bromoadenosine 3',5'-cyclic monophosphate. Pretreatment with the phosphodiesterase inhibitor RO20-1724 or indomethacin did not inhibit the action of ATP. Staurosporin and 3,4,5-trimethoxybenzoic acid 8-(diethylamino)octyl ester significantly attenuated the inhibition of Pf by lower concentrations of ATP. These data suggest that ATP activates nucleotide receptors on the CCT, mobilizing intracellular Ca2+, which inhibits the hydrosmotic action of AVP.
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PMID:ATP inhibits the hydrosmotic effect of AVP in rabbit CCT: evidence for a nucleotide P2u receptor. 806 90


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