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)

Islet-activating protein (IAP), pertussis toxin, is an oligomeric protein composed of an A-protomer and a B-oligomer. There seem to be at least two molecular mechanisms by which IAP exerts its various effects in vivo and in vitro. On the one hand, some of the effects were not significantly affected by acetamidination of the epsilon-amino groups of the lysine residues in the molecule. These include the activities in vitro (1) catalyzing ADP-ribosylation of one of the membrane proteins directly, (2) enhancing membrane adenylate cyclase activity in C6 cells, (3) reversing receptor-mediated inhibition of insulin or glycerol release from pancreatic islets or adipocytes, respectively, and the activities in vivo (4) inhibiting epinephrine-induced hyperglycemia, (5) potentiating glucose-induced hyperinsulinemia, (6) reducing hypertension and increasing the heart rate in genetically hypertensive rats. These activities are concluded to develop as a result of ADP-ribosylation catalyzed by the A-protomer which is rendered accessible to its intramembrane substrate thanks to the associated B-oligomer moiety. Thus, neither the enzymic activity of the A-protomer nor the transporting activity of the B-oligomer needs free amino groups of the lysine residues in the IAP molecule. On the other hand, additional effects of IAP, such as (1) mitogenic, (2) lymphocytosis-promoting, (3) histamine-sensitizing, (4) adjuvant and (5) vascular permeability increasing, were markedly suppressed by acetamidination of the intrapeptide lysine residues. The free epsilon-amino group of lysine would play an indispensable role in the firm (or divalent) attachment of the B-oligomer of IAP to the cell surface that is responsible for development of these activities.
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PMID:Dual mechanisms involved in development of diverse biological activities of islet-activating protein, pertussis toxin, as revealed by chemical modification of lysine residues in the toxin molecule. 638 83

Exposure of rat pancreatic islet membranes to [alpha-32P]-NAD+ in the presence of Bordetella Pertussis toxin (islet-activating protein) reveals the ADP-ribosylation of a peptide with a Mr close to 41 kDa, which corresponds to the alpha-subunit of the guanine nucleotide regulatory protein Ni. Islets removed from rats pretreated with the Bordetella Pertussis toxin display a specific increase in adenylate cyclase responsiveness to GTP and are characterized by a resistance to the inhibitory action of alpha2-adrenergic agonists upon either adenylate cyclase activity or glucose-induced insulin release.
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PMID:Effect of Bordetella pertussis toxin on ADP-ribosylation of membrane proteins, adenylate cyclase activity and insulin release in rat pancreatic islets. 638 72

To facilitate understanding of the advances in health care in Nicaragua since 1979, this discussion examines them within a historical framework. Nicaragua was occupied by US marines almost continuously from 1909-33. In 1933, their withdrawal left in power the US backed National Guard and the 1st dictator, Anastasio Somoza Garcia. Health conditions under the Somoza regime are difficult to evaluate because lack of data and underreporting were the norm. The health care system under Somoza was administered by 23 separate agencies, including the National Social Security Institute (INSS), a national Ministry of Health, independent local health ministries, and autonomous public hospital governing boards. On July 19, 1979, the dictatorship was overthrown in a popular uprising. Somoza left behind a foreign debt of 1.6 billion dollars, which the Sandinista Front for National Liberation (FSLN) needed to honor to qualify for needed loans. Following Somoza's defeat, the new government faced the problem of how to care for the tens of thousands of persons wounded and how to distribute the aid and medical supplies coming in from other countries. The key to achieving these tasks was popular participation and organization. By the early part of 1980, the new government was addressing more directly the organization of the health care system. Unlike the fragmented services under Somoza, health care in the new Nicaragua fell under the control of a unified Ministry of Health (MINSA). In 1980, the FSLN initiated an intensive campaign against illiteracy, 100,000 young Nicaraguans, called "brigadistas," were trained and sent around the country to teach basic reading and writing. In addition, 1 out of 10 was trained in elementary health principles. They were responsible for educating others about hygiene and basic sanitation as well as distributing antimalarial medication. 5 popular Health Campaigns were waged during 1981 against polio; measles, diphtheria, pertussis, and tetanus; rabies; poor sanitation; and malaria. Since women and children make up about 75% of the population, maternal and child health is a priority. The Sandinistas' approach to diarrhea and dehydration, a major cause of morbidity and mortality in children, has been the creation of over 200 oral rehydration units. The purpose of these units, in addition to the oral replacement of an appropriate salt and glucose solution, is to educate health care workers about the prevention and treatment of diarrheal disease. The education of health care workers also has been a priority. With increased access to health services, there is a chronic shortage of supplies and personnel and capital to build new facilities. International aid has been very important to health. Diverting funds away from Nicaraguan destabilization and toward social needs here in the US would have a positive impact on health services for the people of both Nicaragua and the US.
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PMID:Health care in Nicaragua: a social and historical perspective. 659 13

The effect of B. pertussis vaccine on the serum glucose level of mice was investigated. The results show that at least two components in the vaccine interfere with glucose metabolism. A heat-stable component which is assumed to be LPS induced hypoglycemia 3-5.5 h after inoculation, especially in LPS-sensitized mice. A heat-labile component which is possibly equivalent with the LPF/HSF/IAP complex, is responsible for persistence of the hypoglycaemia for at least 6 days. If hypoglycaemia contributes to the neurological side effects after pertussis vaccination both components have to be considered as being responsible for these effects.
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PMID:A biphasic serum glucose response in mice to inoculation with pertussis vaccine. 673 46

The effect of islet-activating protein (IAP) purified from culture medium of Bordetella pertussis was examined in dogs. This was assessed by the levels of pancreatic polypeptide (PP) as well as the responses of plasma insulin and glucagon to a parasympathomimetic agent, bethanechol. Plasma responses of these pancreatic hormones were measured before and 5 days after IAP injection. Although IAP had no significant effect on the bethanechol-stimulated increase in plasma glucose, insulin and glucagon, the PP response to bethanechol was significantly reduced after IAP treatment compared with that before IAP (p less than 0.05). In conclusion, IAP significantly and selectively reduced bethanechol-stimulated PP release in the dog although the mechanism remained to be elucidated.
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PMID:Islet-activating protein (IAP) reduces bethanechol-stimulated release of pancreatic polypeptide in the dog. 675 97

The effect of Bordetella pertussis vaccine on plasma glucose, insulin and glucagon secretion was investigated in normal and alloxan dogs. On the 8th day after the vaccine injection, in normal and alloxan dogs during the infusion of arginine and glucose, the plasma glucose level was lower and the IRI level was higher than in the saline controls. On the other hand, the plasma IRG level showed no significant alloxan dogs this vaccine made the plasma IRG level lower during arginine infusion than in the saline controls and suppressed it significantly during glucose infusion. These effects of the vaccine disappeared on the 30th day after its injection into normal and alloxan dogs. It is suggested that in normal dogs Bordetella pertussis vaccine decreased plasma glucose through the promotion of insulin secretion without any effect on glucagon secretion, while in alloxan dogs this vaccine might alleviate hyperglycemia through the enhancement of insulin and the inhibition of glucagon secretion.
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PMID:Effect of Bordetella pertussis vaccine on glucagon secretion in normal and alloxan dogs. 701 12

A new protein termed islet-activating protein (IAP) has recently been extracted from the culture medium of Bordetella pertussis, and shown to enhance insulin secretion in vivo in rats or in vitro in isolated pancreatic islets due to activation of native calcium ionophores. However, it has not been clarified whether or not IAP enhances the secretion of insulin in human pancreatic islets. In order to examine the effect of IAP on human pancreatic islets, pancreatic tissues were obtained from seven patients who had appeared normal in a glucose tolerance test prior to pancreatectomy. Insulin secretion was significantly increased in IAP treated pancreatic islets by the glucose and the arginine stimuli. It is concluded that IAP enhances the insulin secretion in response to insulin secretagogues in human pancreatic islets, suggesting the possible clinical application of IAP to diabetic patients.
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PMID:Effect of islet-activating protein (IAP) upon insulin secretion from human pancreatic islets. 703 Jul 21

The effects of the alpha 2-adrenergic agonist, clonidine, on the glucagon-stimulated glucose output from serum-free cultures of adult rat hepatocytes were examined in vitro. When hepatocytes were cultured with 10 nM dexamethasone under the serum-free condition, 1 or 10 microM clonidine did not inhibit the glucagon-induced glucose production. In contrast, clonidine dose-dependently inhibited the activity concomitantly with suppression of hepatocyte cAMP production by glucagon when they were cultured with 10 nM dexamethasone and 10 nM insulin. The inhibitory effects of clonidine were completely blocked by prior treatment of hepatocytes with pertussis toxin (100 ng/ml). In addition, forskolin-stimulated cAMP production was also inhibited by alpha 2-adrenergic agonists (clonidine and oxymetazoline) in a dose-dependent manner when hepatocytes were cultured with 10 nM dexamethasone and 10 nM insulin. The inhibitory effects of alpha 2-adrenergic agonists on forskolin-stimulated cAMP production were specifically blocked when they were combined with the alpha 2-adrenergic antagonist yohimbine. Hepatocytes cultured with dexamethasone alone showed no response to the alpha 2-adrenergic agonists. The alpha 2-response was abolished when cycloheximide (0.5 microM) was added to the cultures. These results suggest that insulin develops alpha 2-adrenergic responsiveness through new protein synthesis during the primary culture of adult rat hepatocytes.
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PMID:Expression of alpha 2-receptor-mediated responses by insulin in primary culture of rat hepatocytes. 749 72

Amylin inhibits glucose-induced insulin secretion in the rat pancreas. To study the mechanism by which amylin acts on the B-cell, we have investigated, in the perfused rat pancreas, the effect of synthetic rat amylin (75 pM) on insulin release elicited by secretagogues acting on the B-cell via the adenylate cyclase/cAMP system, i.e., glucagon (10 nM), gastric inhibitory polypeptide (GIP, 1 nM), forskolin (1 microM) and isobutylmethylxanthine (IBMX, 75 microM). In addition, we examined the effect of amylin on GIP-induced insulin release in pancreata from rats pretreated with pertussis toxin, an agent which inactivates certain Gi proteins coupled to adenylate cyclase. Amylin inhibited the insulin response to glucagon (approx. 70%), GIP (approx. 90%), IBMX (approx. 75%) as well as the early phase of forskolin-induced insulin output (approx. 74%). However, amylin failed to modify GIP-induced insulin release in pancreata obtained from pertussis toxin pretreated rats. These results would indicate that the inhibitory effect of amylin on insulin secretion could be, at least in part, attributed to its interfering with the adenylate cyclase/cAMP system. Furthermore, prevention of the inhibitory effect of amylin on GIP-induced insulin output by pertussis toxin pretreatment, supports the concept that amylin can inhibit insulin release via a pertussis toxin-sensitive Gi protein coupled to the adenylate cyclase system.
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PMID:Amylin (islet amyloid polypeptide) inhibition of insulin release in the perfused rat pancreas: implication of the adenylate cyclase/cAMP system. 751 1

The insulin secreting rat Rinm5F cells are often used to study the cytotoxic actions of interleukin-1 (IL-1) on pancreatic beta-cells. We demonstrate here that Rinm5F insulinoma cells express both type I and type II interleukin-1 receptor (IL-1R) mRNAs and gene products. IL-1R agonists, recombinant murine IL-1 alpha (rmIL-1 alpha, 10 ng/ml) and recombinant rat IL-1 beta (rrIL-1 beta, 100 pg/ml or 10 ng/ml) induce the upregulation of mRNA expression for both types of IL-1 receptors (IL-1Rs). This effect of rrIL-1 beta is antagonised by preincubation with recombinant human interleukin 1 receptor antagonist protein (rhIL-1ra, 5 micrograms/ml). Furthermore, this rrIL-1 beta induced upregulation of IL-1R mRNAs is blocked by actinomycin D (7.5 micrograms/ml), whereas cycloheximide (20 micrograms/ml) has no effect. The phorbol ester PMA (20 nM) upregulates the expression of mRNAs both IL-1 receptors, whereas glucose (50 mM) upregulates the expression of the type I IL-1R mRNA only. Pretreatment of cells with pertussis toxin (100 ng/ml) partially blocks the rrIL-1 beta induced expression of mRNA for the type I and, to a lesser extent, the type II IL-1R. Incubation of the cells with rrIL-1 beta also induces a time-dependent expression of c-fos, interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-alpha) mRNAs. Binding studies with 125I-recombinant human IL-1 beta (125I-rhIL-1 beta) indicate that IL-1R gene products, with the ligand binding characteristics of the type I IL-1R, are constitutively present on Rinm5F cells. Treatment with rrIL-1 beta (6h) increases the number of 125I-rhIL-1 beta binding sites on Rinm5F cells. We have also demonstrated that the number of type II IL-1R binding sites increases after induction with rrIL-1 beta (6h), by indirect immunofluorescence using a monoclonal antibody (ALVA 42) raised against the human type II IL-1R. Furthermore, we have sequenced the type II IL-1R cDNA in the rat insulinoma Rinm5F cells. The comparison of the amino acid sequence of the rat type II IL-1R with that of the mouse and human type II IL-1Rs shows 90% and 62% amino acid identity, respectively. The most important difference between the human and murine type II IL-1Rs, and this rat type II IL-1R cDNA, is an open reading frame coding for a six amino acid longer, strongly charged (QIKEMK), cytosolic domain.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Interleukin-1 stimulates the expression of type I and type II interleukin-1 receptors in the rat insulinoma cell line Rinm5F; sequencing a rat type II interleukin-1 receptor cDNA. 752 17


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