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)

Picomol doses of the acetylated derivative of beta-endorphin-(1-31), injected intracerebroventricularly (icv) in mice, reduced the analgesic activity of morphine, etorphine and beta-endorphin-(1-31), while the efficiency of DAGO and DADLE in producing analgesia was enhanced. The effects of the delta agonists DPDPE and [D-Ala2]-Deltorphin II were not altered by this treatment. After alpha N-acetyl beta-endorphin-(1-31) injection, morphine antagonized the analgesia of DAGO. The regulatory effect of alpha N-acetyl beta-endorphin-(1-31) was exhibited when giving the peptide both before (up to 24 h) and after the opioids. Naloxone did not prevent or reverse that modulatory activity; moreover, pretreatment with the acetylated peptide did not change the pA2 value displayed by the antagonist at the mu receptor. The antinociceptive activity of the alpha 2-adrenoceptor agonist clonidine was also increased in mice treated with alpha N-acetyl beta-endorphin-(1-31). The reducing activity of alpha N-acetyl beta-endorphin-(1-31) upon morphine- and beta-endorphin-induced analgesia was not exhibited in mice undergoing treatment with pertussis toxin or N-ethylmaleimide, agents known to impair the function of Gi/Go transducer proteins. However, the enhancing activity displayed by this peptide upon DAGO- DADLE and clonidine-evoked antinociception was still manifested. These results confirm and strengthen the idea of alpha N-acetyl beta-endorphin-(1-31) acting as a non-competitive regulator of mu opioid- and alpha 2-adrenoceptor-mediated supraspinal antinociception. A neural substrate acted on by both receptors (likely Gi/Go transducer proteins) appears to be involved in the effects of that neuropeptide.
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PMID:Further characterization of alpha N-acetyl beta-endorphin-(1-31) regulatory activity, I: Effect on opioid- and alpha 2-mediated supraspinal antinociception in mice. 131 89

The intracerebroventricular (i.c.v.) injection of antisera directed against different sequences of Gs alpha to mice enhanced the antinociceptive potency of the opioids morphine, beta h-endorphin-(1-31) and of the alpha 2-agonist clonidine when studied 24 h later in the tail-flick test. The activity of DAGO, DADLE, DPDPE and [D-Ala2]-Deltorphin II remained unchanged after that treatment. Cholera toxin (0.5 microgram/mouse, i.c.v.), agent that impairs the receptor regulation of Gs transducer proteins promoted comparable changes in the supraspinal analgesia induced by these substances. Six days after a single i.c.v. injection (0.5 microgram/mouse) of pertussis toxin the antinociceptive activity of all the opioids and clonidine appeared diminished. It is concluded that opioids and clonidine promote analgesia after binding to receptors functionally coupled to Gi/G(o) proteins, moreover, the activity of morphine, beta-endorphin and clonidine in this test seems to be counteracted by a process involving activation of Gs alpha transducer proteins.
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PMID:Intracerebroventricular injection of antibodies directed against Gs alpha enhances the supraspinal antinociception induced by morphine, beta-endorphin and clonidine in mice. 144 47

Swaziland is a kingdom with 800,000 inhabitants bordering on Mozambique and South Africa with about 50% of the population under 15 years of age. The experience of a nurse in a small clinic in the course of several years is recounted. Swaziland ranks 3rd in the world in alcohol abuse which often leads to wounds requiring suturing. Penicillin is given prophylactically with a paracetamol preparation for analgesia. As a rule, every injured person will get a .5 ml tetanus injection for prophylaxis. The most serious conditions of polyclinic patients are hepatitis, bilharzia, diarrhea, pellagra, pneumonia, and malnutrition. A great number of patients have sexually transmitted diseases, and the rate of AIDS infection is not known. According to 1 study 60-80% of the population in reproductive age will die of AIDS in the course of a 5-year period. The majority of people are impervious to counseling about their sexual behavior in spite of educational programs on the radio, in schools, and in work places. Condoms are not popular, since they are not considered manly. Pregnant women receive iron and multivitamin tablets in the course of pregnancy. Many pregnant women are anemic, and 70% give birth at home, the rest in a hospital or clinic. During delivery they get no analgesia, and there are few complications. The average weight of the newborn is 3.5 kg, although none of the women are under 150 cm. A little after birth all children are vaccinated with bacillus Calmette-Guerin (BCG) and polio, later with diphtheria-pertussis-tetanus (DPT) and measles.
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PMID:[Nursing under a different sky. Swaziland]. 146 29

Alterations in brain opioid binding and opioid pharmacodynamics following chronic (8-day) naltrexone (NTX) treatment were determined in pertussis toxin (PTX)-treated mice. Intrathecal (IT) and intracerebroventricular (ICV) PTX produced a time-dependent, long-lasting inhibition of morphine (SC) analgesia without modifying basal nociception. Inhibition was maximal 16 days following PTX treatment, and was still observed at 40 days. Relative to placebo controls, NTX treatment produced supersensitivity to morphine analgesia in all control mice and in mice pretreated with PTX 1 day before NTX. Supersensitivity was not observed in 7-day PTX-pretreated mice. [3H][D-Ala2-D-Leu5]enkephalin ([3H]DADLE) and [3H][D-Ala2-MePhe4-Gly(ol)5]enkephalin ([3H]DAMGO) binding sites were increased by NTX treatment in saline- and PTX-pretreated groups. KDs were unchanged. These results indicate that PTX does not alter opioid antagonist-induced receptor upregulation. However, PTX treatment can diminish morphine potency in upregulated and control mice. Therefore, opioid analgesia in control and upregulated mice appears to be mediated by receptors linked to a common PTX-sensitive G-protein. Furthermore, in 7-day PTX-pretreated mice, NTX increased binding sites without altering morphine potency, which suggests that new binding sites can appear without being functionally coupled.
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PMID:Dissociation of opioid receptor upregulation and functional supersensitivity. 165 19

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

The cannabinoid receptor that has been pharmacologically characterized for hypothermia, spontaneous activity, analgesia and catalepsy in rodents is the same pharmacological receptor that inhibits adenylate cyclase in vitro. The inhibition of adenylate cyclase by the cannabinoid receptor results from an interaction with Gi, based on the biochemical kinetic properties of the response, the sensitivity to pertussis toxin ADP-ribosylation, and the thermodynamic characteristics of the response. From precedents based on studies of the well-characterized G protein coupled receptors, rhodopsin and the beta-adrenergic receptor, we can predict the tertiary structure of the cannabinoid receptor. Three sites of potential glycosylation are present on the receptor. However, treatment of N18TG2 neuroblastoma cells with tunicamycin to prevent glycosylation of newly synthesized receptors failed to alter cannabinoid-induced inhibition of cyclic AMP accumulation. The cannabinoid response was rapidly desensitized (within 1/2 h). Treatment of cells with tunicamycin failed to alter agonist-induced desensitization processes. These findings can be more veraciously interpreted as we gain a better understanding of the cellular dynamics of the cannabinoid receptor.
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PMID:The cannabinoid receptor: biochemical and cellular properties in neuroblastoma cells. 180 46

Cholera toxin, an agent that impairs the function of Gs transducer proteins, was injected (0.5 microgram/mouse, icv) and the antinociceptive activity of opioids and clonidine was studied 24h later in the tail-flick test. In these animals, an enhancement of the analgesic potency of morphine, beta-endorphin and clonidine could be observed. Cholera toxin did not modify the antinociception evoked by the enkephalin derivatives DAGO and DADLE. Pertussis toxin that catalyses the ADP ribosylation of alpha subunits of Gi/Go regulatory proteins was given icv (0.5 microgram/mouse). This treatment reduced the analgesic effect of opioids and clonidine. However, while the analgesia elicited by DAGO, DADLE and clonidine was greatly decreased, the effect of morphine and beta-endorphin was reduced to a moderate extent. It is concluded that Gi/Go regulatory proteins functionally coupled to opioid and alpha 2 receptors are implicated in the efficacy displayed by opioids and clonidine to produce supraspinal analgesia. Moreover, these two receptors are susceptible to regulation by a process that might involve a Gs protein.
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PMID:Cholera toxin and pertussis toxin on opioid- and alpha 2-mediated supraspinal analgesia in mice. 185 Apr 93

The present study evaluates the effect of pertussis toxin (PTX) on morphine-induced analgesia and lethality. Mice were injected with 0.2 microgram PTX intracerebroventricularly (i.c.v.) and 0.2 micrograms PTX intrathecally (i.t.) or saline. Mice were tested for morphine-induced analgesia (tail flick) and lethality 16 days later; mice were also examined for pentobarbital-induced mortality. Morphine analgesic potency was decreased by approximately 4-fold in PTX-treated mice compared to controls. Conversely, the lethal potency of morphine was increased by 10-fold in PTX-treated mice compared to controls. PTX treatment did not alter the lethal potency of pentobarbital. Morphine-induced analgesia and lethality were dose-dependently antagonized by naloxone in both PTX and saline-treated groups. The results of this study suggest that morphine analgesia is mediated through PTX-sensitive G proteins. On the other hand, morphine-induced lethality appears to be limited by PTX-sensitive factor(s) since PTX treatment enhanced morphine's lethal potency. The increase in lethal potency of morphine may be due to unmasking of an excitatory opioid receptor mediated effect by PTX.
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PMID:Modification of morphine-induced analgesia and toxicity by pertussis toxin. 203 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

Marijuana and many of its constituent cannabinoids influence the central nervous system (CNS) in a complex and dose-dependent manner. Although CNS depression and analgesia are well documented effects of the cannabinoids, the mechanisms responsible for these and other cannabinoid-induced effects are not so far known. The hydrophobic nature of these substances has suggested that cannabinoids resemble anaesthetic agents in their action, that is, they nonspecifically disrupt cellular membranes. Recent evidence, however, has supported a mechanism involving a G protein-coupled receptor found in brain and neural cell lines, and which inhibits adenylate cyclase activity in a dose-dependent, stereoselective and pertussis toxin-sensitive manner. Also, the receptor is more responsive to psychoactive cannabinoids than to non-psychoactive cannabinoids. Here we report the cloning and expression of a complementary DNA that encodes a G protein-coupled receptor with all of these properties. Its messenger RNA is found in cell lines and regions of the brain that have cannabinoid receptors. These findings suggest that this protein is involved in cannabinoid-induced CNS effects (including alterations in mood and cognition) experienced by users of marijuana.
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PMID:Structure of a cannabinoid receptor and functional expression of the cloned cDNA. 216 65


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