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)

Allosteric regulation of [3H]N-methylscopolamine [( 3H]NMS) and [3H]quinuclidinyl benzilate [( 3H]QNB) dissociation from the m1-m5 muscarinic receptor subtypes was examined in transfected CHO-K1 cells. Half-times of dissociation of [3H]NMS from cell membranes (at 23 degrees) ranged from less than 5 min for the m2 subtype to more than 60 min for the m5 subtype. For [3H]QNB, half-times (at 37 degrees) ranged from 1 hr (m2) to almost 4 hr (m3). The presence of gallamine slowed the dissociation of [3H]NMS from all of the subtypes, with an order of potency of m2 greater than m4 greater than m1 greater than m3 greater than m5. Dissociation of [3H]QNB from m1 and m2 receptors was modulated by gallamine in the biphasic manner that we have described previously for cardiac receptors; that is, low concentrations (1-10 microM) of gallamine accelerated dissociation, while 1 mM gallamine slowed it. Verapamil slowed the dissociation of [3H]-QNB from the m2 receptor in a monophasic manner, while the action of d-tubocurarine was qualitatively similar to that of gallamine. The potency of gallamine in allosterically regulating the m2 receptor was inversely related to ionic strength. Inactivation of pertussis toxin-sensitive G proteins abolished the ability of guanine nucleotides to regulate agonist affinity at the m2 receptor, but had no effect on allosteric regulation of the m2 receptor. These findings indicate that susceptibility to allosteric regulation varies in a complex way across muscarinic receptor subtypes and according to the choice of ligand.
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PMID:Allosteric regulation of cloned m1-m5 muscarinic receptor subtypes. 174 70

Sodium and other monovalent cations (added as chloride salts) inhibited adenylate cyclase of luteinized rat ovary. Sodium chloride (150 mM) inhibited basal enzyme activity by 20%. Sodium chloride inhibition was enhanced to 34-54% under conditions of enzyme stimulation by guanine nucleotides (GTP and its nonhydrolyzable analog 5'-guanylyl imidodiphosphate), fluoride anion, and agonists (ovine luteinizing hormone (oLH) and the beta-adrenergic catecholamine isoproterenol) acting at stimulatory receptors linked to adenylate cyclase. Sodium chloride inhibition was dependent on salt concentration over a wide range (25-800 mM) as well as the concentrations of GTP and oLH. Inhibition by NaCl was of rapid onset and appeared to be reversible. The order of inhibitory potency of monovalent cations was Li+ greater than Na+ greater than K+. The role of individual components of adenylate cyclase in the inhibitory action of monovalent cations was examined. Exotoxins of Vibrio cholerae and Bordetella pertussis were used to determine respectively the involvement of the stimulatory and inhibitory guanine nucleotide-binding regulatory components (Ns and Ni) in NaCl inhibition. Sodium chloride inhibited cholera toxin-activated adenylate cyclase activity by 29%. Ni did not appear to mediate cation inhibition of adenylate cyclase because pertussis toxin did not attenuate inhibition by NaCl. Enzyme stimulation by agents (forskolin and Mn2+) thought to activate the catalytic component directly was not inhibited by NaCl but was instead significantly enhanced. Sodium chloride (150 mM) increased both the Kd for high-affinity binding of oLH to 125I-human chorionic gonadotropin binding sites and the Kact for oLH stimulation of adenylate cyclase by sevenfold. In contrast, NaCl had no appreciable effect on either isoproterenol binding to (-)-[125I]iodopindolol binding sites or the Kact for isoproterenol stimulation of adenylate cyclase. The results suggest that in luteinized rat ovary monovalent cations uncouple, or dissociate, Ns from the catalytic component and, in a distinct action, reduce gonadotropin receptor affinity for hormone. Dissociation of the inhibitory influence of Ni from direct catalytic activation could account for NaCl enhancement of forskolin- and Mn2+-associated activities. On the basis of these results, the spectrum of divergent stimulatory and inhibitory effects of monovalent cations on adenylate cyclase activities in a variety of tissues may be interpreted in terms of differential enzyme susceptibilities to cation-induced uncoupling of N and catalytic component functions.
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PMID:Inhibition of adenylate cyclase from luteinized rat ovary by monovalent cations: roles of the stimulatory guanine nucleotide-binding regulatory component and stimulatory hormone receptor. 312 64

Equilibrium binding isotherms of [3H]diprenorphine in membranes from NG 108-15 cells are consistent with a homogeneous population of binding sites. Upon addition of Na+, Mg2+ and GTP, only a 2-fold reduction in affinity with a minor decrease in the number of sites is observed. Dissociation curves of [3H]diprenorphine, however, are clearly biphasic: in the absence of Na+, Mg2+ and GTP, 80% of the bound ligand dissociates slowly with a t1/2 of 100 min, and only 20% rapidly (t1/2 4.5 min). In the presence of Mg2+, nearly all the binding is found in the slowly dissociating form. Upon the addition of either Na+ or GTP, 20-30% of the binding dissociates more rapidly. The rate constant of the rapidly dissociating form generated by Na+, however, is 2.5 times greater than that induced by the presence of GTP. Thus, the addition of both, Na+ and GTP, converts about 80% of the receptor into a very fast dissociating form (t1/2 1.7 min). Exposure of intact cells to pertussis toxin (10 ng/ml) or treatment of membranes with N-ethyl maleimide (500 microM), strongly reduces the proportion of the slowly dissociating component. Following these treatments, the effect of GTP is reduced or abolished, but that of Na+ remains unaffected. We conclude from these data that the effects of Na+ and GTP are not only distinct in site but also in mechanism of action and that there are three forms of opioid receptors that can be differentiated by their kinetic properties. The slowly dissociating receptor form requires a functional N unit.
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PMID:Effects of sodium and GTP on the binding kinetics of [3H]diprenorphine in NG 108-15 cell membranes. 382 34

Dissociation of an activated alpha-subunit from the beta-gamma complex directly regulates secondary messenger proteins. To address the potential role of G proteins expressed in human fetal cochlea, degenerate oligonucleotide primers corresponding to the 3'-end of the conserved region of alpha-subunits were used for polymerase chain reaction amplification of reverse-transcribed total human fetal cochlear mRNAs; GNAZ and GNAQ were isolated. These two G proteins are unique among the G-protein family because they lack a typical pertussis modification site. GNAZ is expressed in high levels in neural tissue while GNAQ is ubiquitously expressed. We characterized GNAZ expression using Northern blots, tissue in-situ hybridization and immunohistochemistry techniques to elucidate the potential role of this protein in inner ear function. Our data suggest that GNAZ may play a role in maintaining the ionic balance of perilymphatic and endolymphatic cochlear fluids.
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PMID:GNAZ in human fetal cochlea: expression, localization, and potential role in inner ear function. 897 5