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)

Receptor recognition of pertussis toxin is mediated by the B oligomer consisting of subunits S2, S3, 2xS4, and S5. One possible way to interfere with toxin action would be the inhibition of recognition and binding of the cellular receptor(s) by preformed toxin-directed antipeptide antibodies. A prerequisite for this approach is the localization of linear antigenic determinants followed by the identification of inhibitory epitopes. Anti-S2 peptide antibodies have been shown to inhibit binding of the holotoxin to in vitro model receptor systems. For the elucidation of linear antigenic and immunogenic determinants harbored in the S3 subunit, synthetic peptides corresponding to selected linear amino acid sequences of S3 have been prepared and used to raise peptide-specific antibodies in rabbits. All peptides elicited a strong homologous response. Four synthetic peptides reacting with anti-pertussis toxin antibodies (R36-51, R87-95, R134-150, and R147-160) have been identified. Seven synthetic peptides (R1-12, R12-23, R14-29m, R36-51, R95-107, R134-150, and R164-178) induced antibodies recognizing pertussis toxin. Thus, these segments correspond to linear antigenic determinants. Analogous to the S2 subunit, the N terminus of S3 proved to be immunorecessive in the native toxin. The highly homologous S2 subunit was only bound strongly in Western blotting (immunoblotting) by antiserum directed at peptide R164-178, which is identical in the S2 and S3 subunits. A weak recognition of S2 in Western blotting was observed with anti-R95-107 antiserum. The ability of affinity-purified anti-S3 peptide antibodies to interfere with pertussis toxin binding was investigated by hemagglutination of goose erythrocytes as a model receptor system for S3-mediated receptor recognition. Antipeptide antibodies directed at R1-12, R12-23, R14-29m, and R36-51 inhibited hemagglutination of goose erythrocytes. This indicates that the corresponding antigenic regions in the S3 subunit are associated with the formation of the receptor binding domain. Inhibition of B-oligomer-mediated pertussis toxin binding to cellular receptors by preformed antipeptide antibodies of sufficient affinity should not only block the detrimental effects of the S1 subunits, but also interfere with the mitogenic effects attributed to the B oligomer.
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PMID:Identification of linear B-cell determinants of pertussis toxin associated with the receptor recognition site of the S3 subunit. 170 21

Activation of protein kinase C by phorbol esters inhibits the endothelium-dependent relaxations evoked by certain stimuli. The release of endothelium-derived relaxing factor can be evoked by a number of distinct subcellular processes, including activation of a pertussis toxin-sensitive G-protein. The aim of the present study was to determine whether or not the inhibitory effect of phorbol esters on endothelial function was associated with inhibition of the pertussis toxin-sensitive pathway. Rings of canine coronary artery were suspended for isometric tension recording in organ chambers filled with modified Krebs-Ringer bicarbonate solution, gassed with 95% O2-5% CO2 (37 degrees C). Treatment of arterial rings with pertussis toxin (100 ng/ml) or with phorbol myristate acetate (PMA, 10(-8) M) inhibited the endothelium-dependent relaxations produced by UK 14,304, an alpha-2 adrenergic agonist, leukotriene C4 or by NaF, a direct activator of G-proteins, but did not affect the endothelium-dependent relaxations produced by bradykinin or by A23187. If the arterial rings were first treated with pertussis toxin, PMA (10(-8) M) no longer inhibited the endothelium-dependent relaxations to NaF. Increasing the concentration of PMA (to 3 X 10(-8) and 10(-7) M) caused inhibition of responses to bradykinin. At higher concentrations, PMA (3 X 10(-7) and 10(-6)) also inhibited the relaxations evoked by A23187. The endothelium-independent relaxations evoked by nitroglycerin were not affected by PMA (10(-8) to 10(-6)).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibition of endothelium-dependent relaxations by phorbol myristate acetate in canine coronary arteries: role of a pertussis toxin-sensitive G-protein. 189 21

Previous studies have reported the development of vasoconstriction immediately after invasive coronary interventions. Other studies in animals have demonstrated that using oversized balloon angioplasty, vasospasm can be suppressed, even in the presence of endothelial denudation due to important structural alteration in vascular smooth muscle. The regenerated endothelium also appears to be impaired chronically by selective attenuation of in vitro endothelial dependent relaxation related to pertussis toxin-sensitive G proteins. The purpose of this investigation was to verify in vivo and in vitro vasoreactivity to bradykinin (BK) and serotonin (5-hydroxytryptamine; 5-HT) (endothelial dependent agonists) as well as to nitroglycerin (NTG) (exogenous nitric oxide donor) at different times after oversized balloon angioplasty intervention ranging from 1 h to 12 weeks, in normal porcine coronary arteries. BK-induced vasodilatation in vivo was impaired acutely, but it was restored after 4 weeks. Serotonin caused vasoconstriction in vivo that was significantly augmented after 12 weeks. Conversely, endothelium-dependent vasodilatation in vitro to BK and 5-HT remained attenuated during the whole period of follow-up. Finally, relaxation elicited by NTG was reduced in the in vivo experiment until the first week after the procedure. Histological analysis showed severe arterial injury, and complete recovery of endothelial coverage after 4 weeks. In conclusion, this experiment supports evidence for the occurrence of the acute attenuation of vasoresponsiveness and chronic endothelial dysfunction following overstretching coronary balloon angioplasty. Abnormal remodeling associated with the severity of injury may contribute to chronic endothelial dysfunction. Differences found between in vivo and in vitro studies also suggest that multiple endogenous influences present in the former can attenuate the greater endothelial dysfunction demonstrated by endothelial assessment in vitro.
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PMID:Chronic endothelial dysfunction after oversized coronary balloon angioplasty in pigs: a 12-week follow-up of coronary vasoreactivity in vivo and in vitro. 1113 83

To analyze the coupling of Galpha subunits to the rat neurotensin receptor NTS-1 (NTR), fusion proteins were expressed in Escherichia coli with various Galpha subunits covalently linked to the receptor C-terminus. The presence of Galpha(q) or Galpha(i/q), in which the six C-terminal residues of Galpha(i1) were replaced with those from Galpha(q), increased the percentage of receptors in the agonist high-affinity state. This effect was less pronounced for wild-type Galpha(i1) and not observed for Galpha(i/s). Functional coupling of neurotensin receptor to Galpha was demonstrated by neurotensin-induced [(35)S]GTPgammaS binding for the Galpha(q), Galpha(i/q) and Galpha(i1) subunits, but not for Galpha(i/s). Our results extend previous findings of the dual coupling of NTR to pertussis toxin-sensitive and -insensitive G-proteins in Chinese hamster ovary cells with preference for the latter.
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PMID:Functional coupling with Galpha(q) and Galpha(i1) protein subunits promotes high-affinity agonist binding to the neurotensin receptor NTS-1 expressed in Escherichia coli. 1128 4

Nesfatin-1 is a recently identified satiety molecule detectable in neurons of the hypothalamus and nucleus of solitary tract (NTS). Immunohistochemical studies revealed nesfatin-1-immunoreactive (irNEF) cells in the Edinger-Westphal nucleus, dorsal motor nucleus of vagus, and caudal raphe nuclei of the rats, in addition to the hypothalamus and NTS reported in the initial study. Double-labeling immunohistochemistry showed that irNEF cells were vasopressin or oxytocin positive in the paraventricular and supraoptic nucleus; cocaine-amphetamine-regulated transcript or tyrosine hydroxylase positive in arcuate nucleus; cocaine-amphetamine-regulated transcript or melanin concentrating hormone positive in the lateral hypothalamus. In the brainstem, irNEF neurons were choline acetyltransferase positive in the Edinger-Westphal nucleus and dorsal motor nucleus of vagus; tyrosine hydroxylase positive in the NTS; and 5-hydroxytryptamine positive in the caudal raphe nucleus. The biological activity of rat nesfatin-1 (1-82) (100 nm) was assessed by the Ca(2+) microfluorometric method. Nesfatin-1 elevated intracellular Ca(2+) concentrations [Ca(2+)](i) in dissociated and cultured hypothalamic neurons. The response was prevented by pretreating the cells with pertussis toxin (100 nm) or Ca(2+)-free solution and by a combination of the L-type and P/Q-type calcium channel blocker verapamil (1 microm) and omega-conotoxin MVIIC (100 nm). The protein kinase A inhibitor KT 5720 (1 microm) suppressed nesfatin-1-induced rise in [Ca(2+)](i). The result shows that irNEF is distributed to several discrete nuclei in the brainstem, in addition to the hypothalamus and NTS reported earlier, and that the peptide interacts with a G protein-coupled receptor, leading to an increase of [Ca(2+)](i), which is linked to protein kinase A activation in cultured rat hypothalamic neurons.
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PMID:Nesfatin-1: distribution and interaction with a G protein-coupled receptor in the rat brain. 1762 99