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

To determine whether or not the CNS inhibitory activity of eel calcitonin (eCT) on adenylyl cyclase is the endocellular mechanism underlying the antinociceptive effect of the peptide, as shown for morphine analgesia, we administered Bordetella pertussis toxin (PTX) by intracerebroventricular (ICV) injection (0.5 microgram/rat) to block the receptor-mediated inhibition of adenylyl cyclase. In PTX-treated rats there was no change in eCT (2.5 micrograms/rat, ICV)-induced antinociceptive activity (hot-plate test) nor in eCT (100 ng/rat, ICV) inhibition of gastric acid secretion (Shay test) whereas morphine (5 micrograms/rat, ICV) analgesia was significantly reduced. In vitro studies showed no reduction of eCT binding in the CNS of rats treated with PTX in vivo. Moreover, PTX treatment did not change the inhibitory effect of eCT on adenylyl cyclase in isolated membranes from rat striatum in contrast with opiates (DAME and morphine) whose effects were lost. As PTX is known to inactivate the guanidine binding inhibitory protein Gi, these data suggest that a G protein, distinct from the Gi protein involved in the coupling of opiate receptors into a functional response, could be responsible for regulating the intracellular pathways resulting in eCT-induced antinociceptive effect and inhibition of gastric acid secretion.
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PMID:Treatment with pertussis toxin does not prevent central effects of eel calcitonin. 165 2

Numerous experiments have demonstrated that physical stress can alter immunological parameters. However, little attention has been paid to the interrelationship between stress and autoimmune processes. The present study was designed to determine the influence of electric shock and sound stress on the development of experimental allergic encephalomyelitis (EAE). Ten-week-old male DA rats highly susceptible to EAE were used. Rats were subjected to the stress procedure during 19 days either before or after immunization with intradermal injection of 0.1 ml of an emulsion containing guinea pig spinal cord (20 mg/rat) in an equal volume of complete Freund's adjuvant (CFA). In addition, rats received subcutaneous injection of Bordetella pertussis in the dorsum of the same foot. Electric stress procedure consisted of 80 inescapable, unpredictable tail shocks (5 s, 1 mA) delivered at the same time each day. Sound stress procedure consisted of exposure of rats to a 90 dB fire alarm bell which rings 60 times for 5 s during one hour, at the same time of the day. Rats were observed daily for clinical signs of EAE and survived animals were sacrificed on day 20 after immunization. The brain and spinal cord sections were examined histologically for mononuclear cell infiltrates characteristics for EAE. The results clearly indicate that inescapable tail shocks suppressed the appearance and development of EAE when rats were subjected to stress procedure during 19 days after immunization, but not when rats were stressed during 19 day before the induction of EAE. On the other hand, in rats exposed to sound stress there was only delay in the onset of the disease.
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PMID:Stress-induced suppression of experimental allergic encephalomyelitis in the rat. 177 36

Intracerebroventricular injection of pertussis toxin (PTX, 1 microgram/rat) six days before the hot plate test abolished analgesia induced by central morphine. The toxin did not affect analgesia evoked by central neurotensin or ASU 1-7 eel calcitonin. PTX pretreatment also attenuated footshock-induced analgesia (FSIA) delivered to all four paws. When the shock was restricted to the front paws, PTX consistently lowered postshock tail flick latencies, but did not reduce analgesia resulting from shock delivered to the hind paws. It thus appears that PTX-sensitive G-proteins are an essential transduction step needed to initiate the molecular events underlying opiate analgesia evoked by either morphine or shock. In contrast, the signal transduction mechanism subsequent to the stimulation of neurotensin or calcitonin receptors, and to the nonopiate FSIA, appears not to involve PTX-sensitive G-proteins.
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PMID:Pertussis toxin pretreatment affects opiate/nonopiate and stress-induced analgesia differently. 206 92

To find whether the antipropulsive effect of morphine administered intracerebroventricularly (i.c.v.) depends on a G-protein-mediated mechanism, we studied the effect of i.c.v. pertussis toxin (PTX) pretreatment on morphine-induced inhibition of intestinal motility. The influence of PTX was evaluated on intestinal transit (charcoal meal test) and by monitoring of intestinal myoelectrical activity. The antitransit effect of morphine (10 micrograms/rat) was antagonized by about 70% 3, 6, 9 and 12 days after PTX pretreatment (1 microgram/rat) and it was partially restored after 25 days. I.c.v. morphine abolished the regular appearance of the myoelectric migrating complex (MMC) recorded in the rat jejunum and this effect was completely antagonized by PTX pretreatment. When morphine was injected 25 days after PTX, it significantly reduced MMC frequency, confirming the partial recovery seen in the transit experiments. The pertussis toxin-catalyzed ADP ribosylation of a 39-41 kDa substrate in membranes prepared from hypothalamus and midbrain of rats injected with toxin 6 days before was strongly reduced as compared to the controls. On the contrary, after 25 days, ADP ribosylation was the same in treated and control rats. Thus the antipropulsive effect of central morphine could be initiated at receptor sites which interact with G-protein substrates of pertussis toxin.
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PMID:Pertussis toxin modifies the effect of central morphine on rat intestinal motility. 216 Mar 68

Six days after intracerebroventricular pretreatment of rats with pertussis toxin (PTX 0.5 microgram/rat) there was a marked decrease in the antinociceptive effect of morphine, regardless of the route of opioid administration (into the periaqueductal gray matter, intrathecally or intraperitoneally) or the analgesic test used (tail flick and jaw opening reflex). PTX pretreatment also partially attenuated the naloxone-precipitated withdrawal syndrome in morphine-dependent rats, significantly reducing teeth chattering, rearing and grooming. These in vivo findings indicate that G-protein-dependent mechanisms are involved in morphine analgesia and dependence. The biochemical mechanism could be related to ADP ribosylation of Gi coupled to the adenylate cyclase system, but an interaction of PTX with other G-proteins linked to different second messengers or directly to ionic channels cannot be excluded.
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PMID:Pertussis toxin inhibits morphine analgesia and prevents opiate dependence. 231 51

Differential susceptibility to the induction of experimental allergic orchitis (EAO) was examined in Lewis/NCr and Le-R subline rats. Lewis/NCr rats were found to be fully susceptible to the induction of EAO whereas Le-R subline rats were not. Disease resistance exhibited by Le-R rats could be overcome by including Bordetella pertussis in the immunization protocol. However, reversal of resistance with B. pertussis was dependent on the dose of rat testicular homogenate in the inoculum and found to be effective only at lower doses of antigen (10 mg/rat). Disease resistance in Le-R rats as well as B. pertussis-induced reversal of resistance did not appear to be associated with either (1) a significant difference in the number of mast cells in the ductus efferentes, the anatomic location of the earliest inflammatory infiltrates, or (2) an alteration in the phenotypic expression of either innate or B. pertussis-induced sensitivity to vasoactive amines. The results are discussed in the context of the role of B. pertussis in other animal models of organ-specific autoimmune diseases. It is proposed that the phenotypic expression of resistance to EAO in Le-R rats is a result of a mutation in a common regulatory locus affecting susceptibility to multiple autoimmune diseases and whose immunoregulatory action is normally exerted during the sensitization phase of the immune response.
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PMID:Actively induced experimental allergic orchitis in Lewis-resistant (Le-R) rats: reversibility of disease resistance by immunization with Bordetella pertussis. 253 83

The effect of pertussis toxin (PT) on experimental autoimmune uveoretinitis (EAU) induced by immunization with S-antigen was examined in rats. Intravenous administration of PT (2 micrograms/rat) initiated the development of EAU in rats that had been made resistant to the induction of EAU by immunization with S-antigen and complete Freund's adjuvant (CFA). The capacity of PT to promote EAU was also demonstrated by a marked augmentation of the inflammation in EAU eyes of rats susceptible to the induction of EAU. PT was most effective when it was given from the day before to the day after immunization with S-antigen. However the induction of EAU was promoted by the injection of PT even 7 days before and 14 days after immunization. The clinical and histopathological findings of the EAU produced by the additional PT treatment were described and the mechanisms by which PT augmented the induction of EAU were discussed.
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PMID:Experimental autoimmune uveoretinitis (EAU) in rats: abrogation of resistance to the induction and augmentation of the inflammation by pertussis toxin. 278 90

Bovine brain contains two GTP-binding proteins, Gi and Go, which are substrates for ADP ribosylation by pertussis toxin. The Gi protein mediates hormone and GTP inhibition of adenylate cyclase, but the function and the precise tissue distribution of Go are unknown. To immunologically probe the localization of Go, we have purified the Go alpha and G beta, gamma subunits of Go and have raised antibodies against them. The polyclonal anti-Go alpha antibodies obtained were very selective for Go alpha compared to Gi alpha or Gs alpha. The positive Go alpha and G beta, gamma immunoreactivities were investigated in different tissues of vertebrates and invertebrates on immunoblots after gel electrophoresis of the crude membranes. The anti-G beta, gamma antibodies recognized a 35-36-kDa protein in brain of vertebrates such as mammals (rat), avians (pigeon), amphibians (frog), fish (trout), and reptiles (turtle) but not in the invertebrates such as molluscs (snail) and insects (locust). With the anti-Go alpha antibodies a high level of immunoreactivity was detected at molecular weights of 39,000-40,000 in the brain of invertebrates as well as in the central nervous system of vertebrates. Moreover, ADP ribosylation with pertussis toxin occurred in the nervous system of invertebrates. These results suggest that the GTP-binding proteins of invertebrates either are devoid of G beta, gamma subunit or, more probably, possess immunologically different G beta, gamma subunits when compared to those of vertebrates. In the vertebrates, Go alpha immunoreactivity was also present in the peripheral nervous system in areas such as the superior cervical ganglia and sciatic nerve. When examined with the anti-Go alpha antibodies, the neuro-and adenohypophysis exhibited a similar immunoreactivity which was about 6 times lower than in brain. Our antibodies also recognized a 40-kDa protein in human adipocytes but at a concentration 17 times lower than that recognized in brain. Taken together, these data show that the Go alpha subunit is well conserved through evolution and, furthermore, confirm that Go alpha is not strictly limited to the nervous system. This suggests that the protein Go ensures a function required for neuronal activity but also present in some other non-nervous tissues.
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PMID:Immunological localization of the GTP-binding protein Go in different tissues of vertebrates and invertebrates. 310 86

Pertussis toxin catalyzes the ADP-ribosylation of the inhibitory subunit (Ni) of adenylate cyclase. Despite several studies which demonstrate that pertussis toxin influences cyclic AMP accumulation and hormone secretion in normal anterior pituitary cells, the target protein(s) for this toxin in these cells has not been identified. We have examined pertussis toxin mediated ADP-ribosylation in membrane preparations of tumor-derived (235-1, GH4C1, GH3) and normal anterior pituitary cells. Autoradiograms of SDS gels reveal that in the presence of [32P]NAD and pertussis toxin, a 40 kilodalton protein band was labeled in membrane preparations from cells cultured with vehicle. Such labeling was diminished when the cells were exposed to pertussis toxin (35 ng/ml) for 18 hours. Similar results were found in both tumor-derived and normal (monkey and rat) anterior pituitary cells. The pertussis toxin specific band was further resolved into two bands of approximately 39 and 41 kilodaltons. Autoradiograms of two dimensional gels revealed two ADP-ribosylated spots with isoelectric points of 5.7 and 6.2, although the molecular weights appeared identical (approx. 40 kilodaltons). Cholera toxin, which catalyzes the ADP-ribosylation of a 45 kilodalton protein did not prevent labeling of the pertussis toxin-specific band(s) in cells pretreated with cholera toxin. These results suggest that pertussis toxin specifically mediates ADP-ribosylation of the Ni protein in normal anterior pituitary cells.
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PMID:Pertussis toxin mediates ADP-ribosylation of pituitary membrane proteins. 373 93

We studied the effect of intracerebroventricular pretreatment with pertussis toxin and cholera toxin on morphine catalepsy in rats. Pertussis toxin (1 micrograms/rat, two, three and six days before) did not affect catalepsy evoked by central morphine. Cholera toxin (1 micrograms/rat) did not affect morphine catalepsy after 24 h and 48 h, but significantly reduced it (about 60%) after three and five days. Ten days later the morphine response had totally recovered. This effect was selective, since morphine analgesia was not modified. The reduction of catalepsy appeared unrelated to the ability of cholera toxin to raise cAMP levels, as demonstrated by the different time course of changes in striatal cholera toxin-stimulated adenylate cyclase activity. The effect required an intact cholera toxin molecule and did not occur with a similar dose of cholera toxin-B subunit. These findings demonstrate that catalepsy is an opioid effect not linked to pertussis toxin-sensitive G proteins and suggest that the Gs protein might be involved.
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PMID:Cholera toxin antagonizes morphine-induced catalepsy through a cyclic AMP-independent mechanism. 825 25


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