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)

This study compared the effects of endothelin-1 (ET-1), ET-2 and ET-3 on the guinea pig field-stimulated ileum. All ETs (0.3-30 nM) caused graded inhibitions of nerve-mediated responses followed by sustained contractions. The rank order of potencies for the twitch depressor effect (IC50S) was ET-3 = ET-1 greater than ET-2, with ET-3 causing greater maximal inhibition than ET-1 or ET-2. The rank order of potencies for contraction (EC50S) was ET-1 = ET-2 greater than ET-3, with ET-1 causing greater maximal contraction than ET-2 or ET-3. Twitch inhibition by ET-1 (3 nM) was unaffected by indomethacin (5.6 microM), cromakalim (10 microM), glibenclamide (3 microM) or nicardipine (0.1 microM). ET-1-induced contraction was unaltered by tetrodotoxin (0.3 microM), atropine (0.3 microM) or glibenclamide, but was reduced by indomethacin. Cromakalim and nicardipine virtually abolished ET-1-induced contraction. ET-1 (up to 30 nM) did not potentiate submaximal contractions induced by acetylcholine, histamine, bradykinin or substance P. ET-3 relaxed ileal segments precontracted with either acetylcholine (0.3 microM) or histamine (1 microM). Pretreatment of guinea pigs with pertussis toxin (50 micrograms/kg i.p., 6 days beforehand) did not influence either effects of ET-1 on the field-stimulated ileum. Our data suggest that the dual effects of ETs on the guinea pig isolated ileum are mediated by distinct receptors and possibly involve different mechanisms of action. The transient inhibition of responses to field stimulation seems unrelated to activation of ATP-sensitive potassium channels and is rather insensitive to L-type Ca++ channel blockade.
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PMID:Dual effects of endothelins -1, -2 and -3 on guinea pig field-stimulated ileum: possible mediation by two receptors coupled to pertussis toxin-insensitive mechanisms. 137 59

The mechanical tone of the airways is regulated by the autonomic nervous system, partly via the activity of ion channels. Ca(2+)-activated K+ (KCa) channels are densely distributed on tracheal smooth muscle cells. We found that beta-adrenergic agonists can augment KCa channel activity via the alpha subunit of the stimulatory GTP-binding (G) protein of adenylyl cyclase, Gs, linked with beta-receptors, and that muscarinic agonists can suppress the activity of this channel via the inhibitory G protein of adenylyl cyclase (pertussis toxin-sensitive G protein), Gi, linked with muscarinic receptors. These results show that there is a dual regulation system of KCa channels, which involves stimulation of the two receptors. Records of isometric tension from guinea pig tracheas incubated with pertussis toxin and cholera toxin show that regulation of KCa channels mediated by Gi and Gs may be important in the mechanical antagonism by the two receptor agonists, and they show that G proteins coupling between receptors and KCa channels may be important in beta-adrenergic bronchodilation in the treatment of asthma. In a previous study in eight atopic asthmatic patients, pretreatment with a beta-agonist abolished allergen-induced bronchoconstriction with no increment in mean plasma histamine, results that are similar to those obtained with cromyolyn sodium, a membrane stabilizer. The membrane-delimited reaction may be a key process in the autonomic regulation of airway tone. In immediate asthmatic reactions (IAR), histamine release from mast cells, contraction of airway smooth muscle, and transmitter release from post-ganglionic neurons within parasympathetic ganglia are believed to be caused by membrane hypopolarization. Because activation of KCa channels leads to hyperpolarization, beta-agonists that cause membrane hyperpolarization (short acting beta-agonists) may antagonize IAR at the level of the cell membrane. In late asthmatic reactions (LAR), short-acting beta-agonists do not have marked effects. However, recent reports have indicated that long-acting beta-agonists that do not cause hyperpolarization can inhibit LAR. Cromakalim, an ATP-sensitive K+ channel activator, reduces the "morning dip" when it is given orally to patients with nocturnal asthma. These findings show that activation of K+ channels may be useful in therapy of bronchial asthma.
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PMID:[Involvement of G proteins between receptors and KCa channels in the regulation of airway tone by the autonomic nervous system]. 875 94

The influence of the ATP-sensitive K+(KATP) channel opener cromakalim on the antinociception induced by agonists of several receptors coupled to pertussis toxin-sensitive G proteins, clonidine (alpha2 adrenoceptor), baclofen (gamma-aminobutyric acid(B) receptor), morphine (mu opioid receptor) and U50,488H (kappa opioid receptor), was evaluated with a tail-flick test in mice. The subcutaneous administration of clonidine (0.12-2 mg/kg), morphine (0.5-16 mg/kg), baclofen (2-16 mg/kg) and U50,488H (2-16 mg/kg) induced a dose-dependent antinociceptive effect. Cromakalim (8-64 microgram/mouse intracerebroventricularly [i.c.v.]) did not change tail-flick latency in control animals but produced a dose-dependent enhancement of the antinociception induced by clonidine and morphine, and shifted their dose-response curves to the left. These effects of cromakalim were antagonized dose dependently by the K(ATP) channel blocker gliquidone (0.1-8 microgram/mouse i.c.v.). On the other hand, cromakalim (16-64 microgram/mouse i.c.v.) did not significantly enhance the antinociception induced by baclofen and U50,488H and did not shift their dose-response curves. These results suggest that opening of the K(ATP) channels plays an important role in the antinociception mediated by alpha(2) adrenoceptors and mu opioid receptors, but not in that induced by gamma-aminobutyric acid(B) and kappa opioid receptors.
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PMID:Cromakalim differentially enhances antinociception induced by agonists of alpha(2)adrenoceptors, gamma-aminobutyric acid(B), mu and kappa opioid receptors. 878 44