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)

After intravitreal injections of cholera or pertussis toxin (CTX or PTX, 0.5 -1 microgram/eye) into the albino rabbit eye, the in vitro responses of ciliary process adenylyl cyclase (AC) to isoproterenol, vasoactive intestinal peptide (VIP), and forskolin (FSK) were increased 21-40% for PTX, but for CTX-injected eyes AC responses to fluoroaluminate, VIP and FSK decreased 70-50%. The increased responses after PTX suggests that this toxin blocked an inhibitory Gi control of AC that is present in the control tissue. However, prolonged (> 24 hr) in vivo exposure to CTX appears to down-regulate the AC enzyme. In contrast to the in vivo findings, AC responsiveness was unaffected by PTX pre-treatment of membranes in vitro, while CTX pre-treatment increased basal activity (+600%), and the FSK response (+30%), but decreased responsiveness to fluoroaluminate, VIP and isoproterenol by 88-56%. Treatment of ciliary process membranes with 32P-NAD and CTX or PTX followed by SDS-PAGE autoradiography of labelled proteins gave two bands for the G-protein alpha-subunits of Gs (45, 56 kDa) and one broad band centered at 40 kDa for Gi-type subunits respectively. Western blots using specific antibodies showed the presence of Gi type I or III, but no detectable Gi type II or Go in rabbit ciliary processes. We conclude that the changes in adenylyl cyclase enzyme responses after intraocular CTX or PTX may not correlate with cAMP levels and intraocular pressure effects. However, the in vitro biochemical data on AC responses and on G-proteins provide evidence for dual regulation of ciliary process AC by activating and inhibitory G-proteins.
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PMID:Role of G-proteins in ciliary process adenylyl cyclase responses of the albino rabbit eye. 803 85

The prolactin secreting rat pituitary tumor cell line, GH3, expresses high affinity receptors for both vasoactive intestinal peptide (VIP) and somatostatin (SS14). VIP induces prolactin secretion by GH3 cells, an action which is antagonized by SS14. This in vitro model was used to examine the mechanism of action of two synthetic somatostatin analogs, D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-OH (octreotide; SMS 201-995) and cyclo(aminoheptanoyl-Phe-D-Trp-Lys-Thr (benzyl)) (cyclic pentapeptide; CPP). Octreotide and CPP bind to the pituitary somatostatin receptor with lower affinity than does SS14 (KD = 1.3 +/- 1.1; 80 +/- 29; 211 +/- 107 nM for SS14, octreotide and CPP, respectively). SS14 and octreotide were equally effective as inhibitors of VIP-mediated accumulation of cAMP (40% and 45% inhibition, respectively, P < 0.01). SS14 and octreotide also inhibited forskolin-mediated accumulation of cAMP (42% and 40% inhibition of cAMP production, respectively; P < 0.01). The inhibitory action of somatostatin and octreotide on both VIP- and forskolin-mediated cAMP accumulation was blocked by pre-treatment of GH3 cells with pertussis toxin (P < 0.001). Neither SS14 nor octreotide affects the apparent affinity of VIP for its specific receptors on GH3 cells; thus, the inhibitory action of SS14 and octreotide appears to be mediated at the locus of the G-protein-adenylate cyclase complex. In contrast, CPP inhibited VIP-mediated cAMP accumulation slightly, but had no effect on forskolin-mediated cAMP production. Pertussis toxin did not attenuate CPP affects on VIP-mediated cAMP accumulation. However, pre-incubation of GH3 cells with CPP decreased the apparent affinity of receptors for VIP, suggesting that effects of CPP are attributable to interference with VIP binding rather than inhibition at the G-protein-adenylate cyclase complex.
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PMID:Mechanisms of action of long-acting analogs of somatostatin. 809 91

We studied the effect of adenosine on prolactin secretion by the anterior pituitary, and the transduction mechanisms whereby the purine exerts its action. Adenosine inhibited prolactin release in basal and in vasoactive intestinal peptide (VIP)- or TRH-stimulated conditions. Pertussis toxin pretreatment reduced the inhibition of VIP-stimulated prolactin secretion which was induced by adenosine, while it completely abolished the effect of the purine on TRH-evoked prolactin release. In membrane preparations of anterior pituitary cells, adenosine reduced the adenylate cyclase activity stimulated by VIP. Such an inhibition was not blocked by pertussis toxin pretreatment. Furthermore, the purine reduced TRH-stimulated inositol phosphate production in cultured anterior pituitary cells, an effect that was reversed by pretreatment with pertussis toxin. In addition, the nucleoside did not significantly affect the TRH-induced rise in intracellular calcium. In conclusion, our data show that adenosine inhibits prolactin secretion, acting on purinergic receptors coupled to the adenylate cyclase enzyme and phospholipase C. The effect of the nucleoside on adenylate cyclase seems to be achieved either by the involvement of an adenosine receptor coupled to the catalytic subunit of the enzyme via a pertussis toxin-sensitive G protein, or by the activation of a site directly coupled to the catalytic subunit of the adenylate cyclase (the P site). Its effect on phospholipase C seems to be mediated by a purinergic receptor coupled to the intracellular effector via a pertussis toxin-sensitive G protein.
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PMID:Direct effect of adenosine on prolactin secretion at the level of the single rat lactotroph: involvement of pertussis toxin-sensitive and -insensitive transducing mechanisms. 814 40

We reported previously that in homogenates of rat olfactory bulb muscarinic and opioid receptor agonists stimulate adenylyl cyclase activity. In the present study we show that carbachol (CCh) and Leu-Enkephalin act synergistically with vasoactive intestinal peptide (VIP) and corticotropin-releasing hormone (CRH), but not with l-isoproterenol, in increasing cyclic AMP formation. The synergistic interaction consists of an increase in the maximal adenylyl cyclase activation without a significant change in the potency of each agonist. CCh also fails to affect 125I-CRH binding to olfactory bulb membranes. The synergism requires micromolar concentrations of GTP. Substitution of the stable GTP analog guanosine 5'-O-(3'-thiotriphosphate) for GTP allows the CRH stimulation, but abolishes the CCh enhancement of both basal and CRH-stimulated enzyme activities. Moreover, in vivo treatment of olfactory bulbs with pertussis toxin completely prevents the muscarinic and opioid effects. Thus, the synergistic interaction appears to result from opioid- and muscarinic-induced activation of a pertussis toxin-sensitive GTP-binding protein which may potentiate the adenylyl cyclase stimulation by the stimulatory GTP-binding protein activated by either VIP or CRH receptors.
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PMID:Synergistic interaction of muscarinic and opioid receptors with GS-linked neurotransmitter receptors to stimulate adenylyl cyclase activity of rat olfactory bulb. 824 71

In order to study the activation mechanism of heterotrimeric G-proteins by agonist-liganded receptors, GTP gamma S binding to membranes was measured in rat adenohypophyseal cells after addition of dopamine (DA) or vasoactive intestinal peptide (VIP), which, respectively, inhibit and activate pituitary adenylyl cyclase. G-protein subunit present in anterior pituitary cells was characterized by either ADP-ribosylation catalysed by Bordetella pertussis and cholera toxins or by immunoblot using specific antisera. Binding of GTP gamma S was found to depend upon GTP gamma S and Mg2+ concentrations; it was sensitive to pretreatment of the cells with cholera and Bordetella pertussis toxins (IAP). DA increased binding of the nucleotide. Paradoxically, VIP decreased the rate of GTP gamma S binding; the effect was suppressed by prior treatment of the cells with either cholera toxin or IAP. VIP also increased [33P]ADPribose incorporation in Gi/Go-proteins catalysed by IAP. Forskolin was also able to decrease GTP gamma S binding, thus suggesting that the binding of forskolin with the adenylyl cyclase catalytic unit might activate Gs proteins through an increased interaction between Gs and adenylyl cyclase. Taken together, these results suggest that VIP, as well as forskolin, may both accelerate the activation of Gs and suppress the inhibitory effect of activated Gi/Go-proteins. Interactions between Gs and Gi/Go subunits mediated by beta gamma and/or adenylyl cyclase might thus result in a kinetic coupling of transduction pathways involving distinct G-proteins.
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PMID:Vip-induced cross-talk between G-proteins in membranes from rat anterior pituitary cells. 849 23

The influence of activation of protein kinase C (PKC) and cyclic AMP on noradrenaline (NA) release in the neurosecretory rat pheochromocytoma PC12 cell line was investigated. External ATP induced [3H]NA release from prelabeled PC12 cells, in the presence of extracellular CaCl2. The potency order of ATP analogs was adenosine 5'-O-(gamma-thiotriphosphate) > or = ATP > 2-methylthio ATP > 2',3'-O-(4-benzoyl)benzoyl ATP. alpha,beta-Methylene ATP, beta gamma-methylene ATP, and 8-bromo ATP were inactive. Neither ADP, GTP, nor ITP was active. The addition of phorbol 12-myristate 13-acetate (PMA) or agents elevating the cyclic AMP content, such as vasoactive intestinal peptide (VIP) or an adenosine analog, also stimulated [3H]NA release. Not only high K(+)- but also ATP-stimulated [3H]NA release was enhanced by co-addition with PMA or agents elevating the cyclic AMP content. PMA and VIP had no effect on the cytosolic free Ca2+ concentration ([Ca2+]i) or on the ATP-stimulated [Ca2+]i rise, although both stimulatory effects on [3H]NA release were dependent on extracellular CaCl2. The addition of PMA stimulated [3H]NA release dose-dependently, and enhanced 300 microM (maximal dose) ATP-stimulated [3H]NA release without changing the affinity for ATP. The effect of PMA was inhibited by PKC inhibitors such as calphostin C and in PKC-depleted cells, and potentiated by elevation of cyclic AMP. These data suggest that the process of ATP-stimulated NA release, not ATP-stimulated Ca2+ influx, is regulated by the dual, PKC- and cyclic AMP-dependent mechanisms, positively and independently. Treatment with pertussis toxin had no effect on the ATP-stimulated [Ca2+]i rise or [3H]NA release.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of protein kinase C and A activation on ATP-stimulated release of [3H]noradrenaline from PC12 cells. 854 66

Because some endothelial cells contain a high density of functional vasoactive intestinal peptide (VIP) receptors, it is possible that in some cases, relaxation of blood vessels by VIP is mediated by endothelium. We showed earlier that VIP inhibited inwardly rectifying K+ currents (IKin) in cultured bovine pulmonary artery endothelial cells. Our studies now provide both direct and indirect evidence that activation of these receptors does not occur through an elevation of cAMP level in these cells. Isoproterenol increased cAMP in endothelial cells from 30% to 35% over the basal levels. In contrast, VIP did not elevate cAMP in endothelial cells and even decreased it in some instances. In whole-cell patch-clamp experiments, isoproterenol weakly inhibited the IKin (about 80% less than VIP). The magnitudes of effects evoked by other activators of the cAMP cascade (forskolin, cAMP analogs) on this current were intermediate between those of VIP and isoproterenol. Although cAMP elevation can reduce the IKin current in endothelial cells, it is not responsible for the inhibitory effect of VIP on this current. We demonstrated that VIP receptors interact with the IKin channels through a G protein. Guanosine 5'-(3'-O-thiotriphosphate, a nonhydrolyzable GTP analog, or cholera toxin inhibited these channels in a manner similar to inhibition by VIP. The activity of the IKin channels was pertussis toxin-insensitive. Furthermore, guanosine-5'-O-(2-thiodiphosphate) blocked the VIP receptor-mediated effect on the IKin. Our results suggest that VIP receptors couple to IKin channels through a G protein.
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PMID:A G protein, not cyclic AMP, mediates effects of VIP on the inwardly rectifying K+ channels in endothelial cells. 863 38

GTP-binding proteins are key elements in coupling receptors to various effector systems. Using ADP-ribosylation by cholera (CTX) and pertussis (PTX) toxins and an immunodetection technique, we investigated the G protein expression profile in smooth muscle of stem villi vessels obtained from human term placentae. In placental vascular smooth muscle, we report the presence of two CTX-protein substrates of 42 and 45 kDa recognized by Gs alpha antibodies, and three Gi alpha isoforms, substrates of PTX, identified as Gi1 alpha, Gi3 alpha (two proteins of 41 kDa) and Gi2 alpha (a 40-kDa protein). We also characterized another target of PTX, a 40-kDa Go alpha-immunoreactive protein and detected the PTX-insensitive Gq-Gi1 alpha proteins. To assess the functional significance of the G alpha proteins identified in this tissue, we measured the adenylyl cyclase activity in the presence of guanyl nucleotides alone or with increasing concentrations of vasoactive intestinal peptide (VIP), and examined whether VIP-bound sites, in the presence of GTP gamma S, promote the release of G alpha proteins from the membranes of vascular smooth muscle. At low concentrations (0.1 nM to 0.01 microM), guanyl nucleotides stimulated adenylyl cyclase activity in a dose-dependent manner, while at higher concentrations (10 microM to 1 mM) the stimulation rate of cAMP production by guanyl nucleotides decreased. In a dose-dependent manner, VIP in the presence of GTP gamma S increased adenylyl cyclase activity and specifically promoted the release of both Gs alpha isoforms. In contrast, the release of Gi1 and Gi2 alpha isoforms was not significantly increased in the presence of VIP, while GTP gamma S alone stimulated their release. Our data show physical evidence of the activation of Gs proteins by VIP-bound membrane receptors, resulting in dissociation and release of Gs alpha subunits in the soluble fraction. They assess the specific coupling of the two Gi alpha isoforms to VIP receptors in smooth muscle wall of placental stem villi vessels. It would be of interest to investigate whether changes in Gs alpha expression and/or function are associated with the placental angiogenesis process during pregnancy.
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PMID:G protein expression in human fetoplacental vascularization. Functional evidence for Gs alpha and Gi alpha subunits. 876 39

Although vasoactive intestinal peptide (VIP) exerts many of its effects through stimulation of adenylyl cyclase, there is increasing evidence that other signaling pathways may contribute to its action. The role of inhibitory G proteins (Gi) in VIP-mediated signaling in the lung was assessed by a combination of equilibrium-binding and covalent cross-linking studies. Pertussis toxin treatment of rat lung membranes reduced the high affinity binding of 125I-VIP, implicating a member of the Gi family in signaling from the VIP receptor. The particular G protein involved was identified as Gi3 through capture of a VIP/receptor/ Gi3 ternary complex by covalent cross-linking. There was a progressive rise with increasing VIP concentration in formation of the complex reported by the cross-linking strategy. Guanine nucleotides and an anti-G alpha i3 antiserum suppressed formation of the VIP/receptor/Gi3 ternary complex, demonstrating its functional nature in native lung membranes. Inhibition of high affinity 125I-VIP binding by the anti-G alpha i3 antiserum verified this functionality. Taken together, these data suggest that receptor/ Gi3 coupling makes a significant contribution to VIP-mediated signaling in the lung and illustrate the value of covalent cross-linking as a strategy to define receptor/G protein complexes that arise under conditions in which the stoichiometry and microdomains of the native cell membrane are preserved.
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PMID:Direct evidence for functional coupling of the vasoactive intestinal peptide receptor to Gi3 in native lung membranes. 879 3

An immunoregulatory role for vasoactive intestinal peptide (VIP) is suggested by the high concentrations in subsets of neurons supplying lymphoid organs and by the capacity of VIP to affect T lymphocyte functions. The Tsup-1 line of human T lymphoblastoma cells expresses both type I and type II G protein-coupled VIP receptors (Rs), as shown by detection of the encoding mRNAs with reverse transcription-polymerase chain reaction analyses. Northern blot quantification of the relative amounts of mRNA encoding the two VIPRs in Tsup-1 cells indicated that type II predominates over type I, as it does in human blood CD4+ T cells. Tsup-1 cells bound 125I-VIP to 8.95 x 10(4) high-affinity sites/cell (Kd = 6.0 nM) and 7.45 x 10(5) low-affinity sites/cell (Kd = 210 nM). VIP increased [cAMP]i in Tsup-1 cells (EC50 = 14.4 nM) and stimulated a rapid and transient increase in [Ca2+]i (EC50 = 30 nM). Functional coupling of G proteins to type II VIPRs was suggested by the change in binding of 125I-VIP to Tsup-1 cell membranes from two sites with Kd values of 3.8 and 109 nM to one site of Kd 30 nM by GTP-gamma-S and the suppression by pertussis toxin of increases in [Ca2+]i evoked by VIP. The VIP antagonists, VIP4-28 and (4-Cl-D-Phe6-Leu17) VIP, inhibited 125I-VIP binding by type II VIPRs, as well as VIP-elicited increases in [Ca2+]i and [cAMP]i. Type II VIPRs thus are the major transducers of VIP signals to a subset of human T cells.
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PMID:Predominant expression of type II vasoactive intestinal peptide receptors by human T lymphoblastoma cells: transduction of both Ca2+ and cyclic AMP signals. 892 82


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