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)

Development of an enriched cultured cell system allowed us to investigate the mechanism of cholinergic inhibition of somatostatin release stimulated by adenosine 3',5'-cyclic monophosphate (cAMP) and Ca2+-protein kinase C-dependent pathways of cell activation. After a 24-h culture on rat tail collagen, D-cells, quantified by immunohistochemistry, were 18-fold enriched compared with unelutriated dispersed cells. Somatostatin release from cultured cells was expressed as a percent of the somatostatin released by a specific stimulus in control cells. Under basal conditions release of somatostatin was 2.3 +/- 0.6% of the total cell content. Epinephrine (1 microM) and cholecystokinin octapeptide (10 nM) increased somatostatin release to 6.98 +/- 1.25 and 10.72 +/- 1.64%, respectively. Carbachol (1 microM) completely inhibited somatostatin release stimulated by epinephrine and reduced cholecystokinin octapeptide-stimulated release to 75% of control levels. Carbachol inhibition of the response to both epinephrine and cholecystokinin octapeptide was totally prevented by 5 h of treatment of the cells with pertussis toxin (300 ng/ml). Somatostatin release in response to the diterpene forskolin (10 microM), dibutyryl cAMP (300 microM), the phorbol ester beta-phorbol 12-myristate 13-acetate (0.1 microM), and the calcium ionophore A23187 (1 microM) was also inhibited by carbachol and prevented by pertussis toxin pretreatment. The ADP-ribosylase inhibitor isonicotinamide (1 mM) selectively blocked the effect of pertussis toxin without altering other stimulatory or inhibitory responses. These data are consistent with the view that carbachol inhibits somatostatin release at guanyl nucleotide-binding protein and/or another pertussis toxin-sensitive site.
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PMID:Pertussis toxin-sensitive cholinergic inhibition of somatostatin release from canine D-cells. 290 2

Pancreatic islets were maintained in culture with or without islet-activating protein (IAP), which is a new protein purified from culture medium of Bordetella pertussis. These cultured islets (IAP-treated or control) were then incubated for 30 min in IAP-free medium with various insulin secretagogues. During incubation, much more insulin was released from IAP-treated islets than control islets in response to glucose, arginine, glucagon, and sulfonylurea. IAP was effective in this regard when added to cultures at concentrations higher than 0.01 ng/ml; the effect was dependent on concentration up to 100 ng/ml. Enhanced insulin secretion was associated with accumulation of cyclic AMP when breakdown of the nucleotide was prevented by a methylxanthine. Epinephrine caused marked inhibitions, via alpha-adrenergic receptors, of glucose-induced insulin release, cyclic AMP accumulation and 45Ca uptake in control islets but did not in IAP-treated islets during incubation. None of these effects of IAP pretreatment were observed unless the medium for incubation was supplemented with Ca ions. 45Ca ion flux through the islet cell membrane was accelerated by the IAP treatment; conceivably, IAP was effective in causing sustained activation of native calcium ionophores on the membrane, which would be responsible for the enhanced insulin and cyclic AMP responses characteristic of IAP-treated islets.
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PMID:In vitro effects of islet-activating protein on cultured rat pancreatic islets. Enhancement of insulin secretion, adenosine 3':5'-monophosphate accumulation and 45Ca flux. 616 8

Islet-activating protein (IAP) is a substance purified from the culture medium of Bordetella pertussis, and its main action is characterized by the enhancement of secretory response to glucose and other stimuli in pancreatic islet. In this experiment, the effect of IAP on epinephrine-induced secretion of immunoreactive insulin (IRI) and glucagon (IRG) was investigated in normal dogs. Epinephrine suppressed IRI secretion and it had a little increment to IRG secretion in control group, while IRI and IRG secretions were significantly increased by epinephrine in IAP pretreated group. Using beta-blocker (Propranolol) with epinephrine, these increments of IRI and IRG secretions in IAP pretreated group were abolished. However, using alpha-blocker (Phentolamine) with epinephrine, these secretions of IRI and IRG in IAP pretreated group were much more increased than epinephrine alone induced secretions. Blood glucose levels were lower in IAP pretreated group than in control group throughout the loading tests in all of the experiments. These findings suggest that (1) IAP decreases blood glucose level and (2) IAP enhances epinephrine-induced secretion of insulin and glucagon by acceleration of beta-adrenergic effect and by reduction of alpha-adrenergic suppression in dogs.
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PMID:Islet-activating protein (IAP)-induced adrenergic modulation of pancreatic A and B cell in dogs. 637 Aug 19

Adenylate cyclase of the membrane-rich fraction of 24-h cultured islets was inhibited by epinephrine via alpha-adrenergic receptors. Epinephrine was inhibitory only when the enzyme was activated by GTP; the degree of inhibition was highly proportional to the degree of GTP activation. Adenylate cyclase of islets cultured with islet-activating protein (IAP), one of the pertussis toxins, was less susceptible to epinephrine inhibition. The degree of the inhibition was markedly reduced without changes in potency of the catecholamine and in GTP dependence after IAP treatment. None of the other kinetic properties of the enzyme including the affinity for substrate, sensitivity to guanine nucleotide and fluoride activation, and cholera toxin-induced modification of enzymic activity were affected by treatment of islets with IAP, suggesting that neither the catalytic nor the GTP-regulatory component of the membrane adenylate cyclase complex is the site of IAP action. Slight activation of the enzyme by glucagon or adenosine tended to be enhanced by IAP treatment. Thus, a mechanism whereby membrane receptors are linked to adenylate cyclase appears to be modified by exposure of islet cells to IAP.
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PMID:Islet-activating protein. A modifier of receptor-mediated regulation of rat islet adenylate cyclase. 702 47

B. pertussis vaccine or pulmonary infection produced marked hyperinsulinaemia in mice relative to controls (e.g. control 32 mU/1; B. pertussis infected 113 mU/1). This was associated with a modest relative hypoglycaemia (15-25%). The hyperinsulinaemia was observed only when blood was collected from mice anaesthetized with ether, pentobarbitone, or trichloroethylene but not from unanaesthetized animals. Ether-induced hyperinsulinaemia in B. pertussis was transient. Adrenaline produced marked hyperinsulinaemia in B. pertussis-infected mice whereas it tended to produce hypoinsulinaemia in control animals. The hyperinsulinaemic effect of ether anaesthesia in B. pertussis-infected mice was significantly reduced by beta-adrenoceptor blockade using propranolol. It is suggested (a) that pertussis-infected or vaccinated mice are not chronically hyperinsulinaemic but show elevated insulin concentrations only when subjected to an additional stimulus; (b) that hyperinsulinaemia produced by anaesthesia in pertussis-treated mice is secondary to an altered responsiveness of the insulin-secreting cells to this stimulus; (c) that part of this stimulus may be due to catecholamines released during anaesthesia.
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PMID:Bordetella pertussis-induced hyperinsulinaemia without marked hypoglycaemia: a paradox explained. 702 74

The purpose of this study was to examine the hypothesis that the calcium channel blocker verapamil modulates catecholamine-induced arrhythmias in brain and to explore potential mechanisms of action. Wistar rats with catheters previously inserted in the lateral cerebral ventricle and femoral artery received verapamil 10 or 50 micrograms/kg or the diluent (intracerebroventricularly, i.c.v.) into the lateral cerebral ventricle. Epinephrine was infused to produce arrhythmias. Onset of ventricular arrhythmias, premature ventricular complexes (PVCs), occurred at a significantly (p < 0.05) higher epinephrine dose after the higher dose of verapamil. Development of fatal arrhythmias, mainly ventricular tachyarrhythmias, occurred at significantly (p < 0.05) higher epinephrine concentrations with verapamil 50 micrograms/kg i.c.v. as compared with controls. Comparison of the two enantiomers of verapamil (50 micrograms/kg i.c.v.) showed that S(-)verapamil had the same effect as the racemic mixture whereas R(+)verapamil was intermediate between the control and S(-)verapamil. The antiarrhythmic action of verapamil could not be explained by alteration of the blood pressure (BP) response to epinephrine. Endogenous opioids were implicated in this action of verapamil because the (-)enantiomer of naloxone, which is an opioid antagonist, significantly (p < 0.05) antagonized the antiarrhythmic effects of centrally administered verapamil to suppress epinephrine-induced arrhythmias. In contrast the (+)enantiomer of naloxone did not alter verapamil-induced increase in arrhythmia threshold. Pretreatment with pertussis toxin i.c.v. antagonized the effects of verapamil. Verapamil did not alter the cyclic AMP response to isoproterenol in lymphocytes isolated from Wistar rats not exposed to any other drugs.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Verapamil has antiarrhythmic effects that are mediated in brain through endogenous opioids. 752 66

Human erythroleukaemia (HEL) cells were investigated to characterize their alpha 2-adrenoceptor and imidazoline receptor sites. Membranes from HEL cells bound [3H]2-(2-methoxy-1, 4-benzodioxan-2yl)-2-imidazoline ([3H]RX821002) in a saturable and specific manner with a KD of 0.64 +/- 0.07 nM and a Bmax of 126 +/- 4 fmol/mg protein. [3H]RX821002 was displaced from HEL membranes by adrenergic drugs with the order of potency being yohimbine approximately oxymetazoline >> prazosin = 2-[2-[4-(o-methoxyphenyl)piperazin-1-yl]ethyl]-4,4-dimethyl- 1,3(2H,4H)-isochinolindione HCl (ARC 239), consistent with this site being an alpha 2A-adrenoceptor. HEL membranes also bound [3H]idazoxan in the presence of adrenaline to block alpha 2-adrenoceptors. This binding was saturable and specific with a KD of 3.5 +/- 1.0 nM and a Bmax of 31 +/- 6 fmol/mg protein. Adrenergic drugs from both the phenylethylamine and imidazoline classes increased high-affinity GTPase activity, an index of activation of regulatory heterotrimeric guanine-nucleotide binding proteins (G-proteins), and produced increases in cytosolic free calcium concentration ([Ca2+]i). The effects of these agonists in both systems were abolished by pertussis toxin pretreatment, and oxymetazoline and clonidine were antagonists. The potency of adrenergic drugs to inhibit 5-bromo-6-(2-imidazolin-2-ylamino)-quinoxaline (UK 14304)-induced increases in [Ca2+]i was yohimbine approximately oxymetazoline >> ARC 239, consistent with the binding data and an action at alpha 2A-adrenoceptors. No evidence was found for a role of imidazoline receptors in stimulating G-proteins or modulating [Ca2+]i. The adrenergic agonist-induced increases in [Ca2+]i were due to both release of Ca2+ from intracellular stores and entry of extracellular Ca2+. Ca2+ entry was blocked by 1-(beta-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenylethyl)-1H- imidazole hydrochloride (SKF 96365), but not by nitrendipine. Adrenaline also stimulated Mn2+ entry in HEL cells. Taken together, these results suggest that HEL cells have alpha 2A-adrenoceptors that activate non-selective cation channels via pertussis toxin-sensitive G-proteins, i.e. Gi-proteins.
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PMID:Alpha 2A-adrenoceptors mediate activation of non-selective cation channels via Gi-proteins in human erythroleukaemia (HEL) cells. No evidence for a functional role of imidazoline receptors in modulating calcium. 753 Sep 55

Morphological analysis of hormone content and functional assessment of hormone secretion were conducted in beta TC-6 cells, an insulin-secreting cell line derived from transgenic mice expressing the large T-antigen of simian virus 40 (SV40) in pancreatic beta-cells. We observed by immunohistochemistry and confocal microscopy that beta TC-6 cells contain abundant insulin and small amounts of glucagon and somatostatin (SRIF). Glucagon usually co-localized with insulin, whereas cells containing SRIF did not contain insulin or glucagon. Static incubation and perifusion experiments demonstrated that beta TC-6 cells at passage 30-45 secrete insulin in response to glucose. In static incubations, maximal stimulation was achieved for glucose concentrations > 2.8 mmol/l glucose, and the half-maximal effect was observed at 0.5 mmol/l. Maximal stimulation was four times greater than HIT-T15 cells at passage 72-81, although HIT cells had a greater response over their basal levels. The magnitude of the insulin response to glucose in perifusion was 1,734 +/- 384 pmol.l-1. min and was 4.6-fold greater in the presence of 3-isobutyl-1-methylxanthine. Low amounts of glucagon were released in response to amino acids. Epinephrine (EPI), and to a lesser extent SRIF, inhibited phasic glucose-induced insulin secretion. A major portion of these inhibitory effects was mediated by pertussis toxin-sensitive substrates. Immunoblots detected the presence of the G-proteins Gi alpha 2, Gi alpha 3, and Go alpha 2. These results indicate that beta TC-6 cells are a glucose-responsive cell line in which insulin exocytosis is physiologically regulated by EPI and SRIF through Gi/Go-mediated mechanisms.
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PMID:Morphological and functional characterization of beta TC-6 cells--an insulin-secreting cell line derived from transgenic mice. 753 32

Epinephrine stimulation of rat alpha 2D, alpha 2B, and alpha 2C adrenergic receptor subtypes, expressed stably in Chinese hamster ovary (CHO) cells, caused a rapid, transient activation of mitogen-activated protein kinase (MAPK), with subtype-specific different efficiencies. The order of activation was CHO-2B approximately CHO-2D much greater than CHO-2C. Pertussis toxin blocked the stimulation of MAPK enzymatic activity and the parallel MAPK phosphorylation, demonstrating that these responses are mediated by pertussis toxin-sensitive Gi proteins. Contrary to what has been reported for the alpha 2A subtype expressed in rat-1 fibroblasts, epinephrine did not cause any detectable activation of p21ras in the CHO transfectants. Furthermore, combined application of epinephrine and phorbol myristate acetate had a potent cooperative but not additive effect in clones CHO-2D and CHO-2B but not in CHO-2C, suggesting that protein kinase C is probably differently involved in the signaling by the three alpha 2 receptor subtypes. These results show that in CHO cells, the different alpha 2 adrenergic receptor subtypes utilize differential pathways to activate MAPK in a p21ras-independent way.
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PMID:Alpha 2 adrenergic receptor subtypes expressed in Chinese hamster ovary cells activate differentially mitogen-activated protein kinase by a p21ras independent pathway. 787 81

The ability of agonist-occupied alpha 2D-adrenergic receptors to activate G proteins was measured in membranes from PC-12 cells stably expressing the cloned receptor, using guanosine-5'-O-(3-[35S]thio)triphosphate ([35S]GTP gamma S) binding as an endpoint. Epinephrine (EPI) stimulated [35S]GTP gamma S binding in a Mg(2+)-dependent manner, showing both micromolar and millimolar cation affinities. Prior treatment of cells with pertussis toxin completely eliminated the EPI stimulation. The presence of GDP decreased basal [35S]GTP gamma S binding and increased the proportion of EPI-stimulated binding. Increasing concentrations of Na+ also reduced basal [35S]GTP gamma S binding but had less effect on EPI-stimulated binding, such that the agonist response was proportionately greater at higher Na+ levels. In saturation binding studies with [35S]GTP gamma S only low affinity binding was observed in the presence of 100 mM Na+, whereas in the absence of Na+ a high affinity component was also present, indicating a Na(+)-regulated receptor/G protein interaction. EPI induced high affinity [35S]GTP gamma S binding in the presence of Na+ and increased the affinity of the high affinity component under Na(+)-free conditions. The selective alpha 2-adrenergic antagonist rauwolscine produced rightward shifts of EPI dose-response curves and decreased the basal level of [35-S]GTP gamma S binding across the same range of concentrations. The extent of decrease was dependent upon the alpha 2-adrenergic receptor expression level, indicating that alpha 2-adrenergic receptors contribute to basal G protein activation in the absence of agonist. The ability of rauwolscine to decrease basal [35S]GTP gamma S binding was diminished as the level of Na+ was increased, suggesting that both agents act to reduce receptor/G protein interaction, by distinctive mechanisms. alpha 2-Adrenergic receptor antagonists reduced basal G protein activation with a rank order for maximal effectiveness that was different from their receptor binding affinities. These results support the existence of precoupling between alpha 2D-adrenergic receptors and G proteins; coupling can be diminished by both Na+ and antagonists, whereas agonists increase the efficiency of receptor/G protein coupling.
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PMID:Determinants of alpha 2-adrenergic receptor activation of G proteins: evidence for a precoupled receptor/G protein state. 814 37


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