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)

Application of a muscarinic agonist to the extracellular surface of membrane patches from airway smooth muscle cells resulted in an inhibition of calcium-activated potassium (KCa) channels in outside-out patches. Methacholine (50 microM) inhibited channel activity at physiological cytosolic calcium concentrations and resulted in a marked shift in channel open-time kinetics. In inside-out patches, KCa channels were inhibited upon addition of GTP (100 microM) when methacholine was present in the patch pipette. Muscarinic inhibition was blocked when guanosine 5'-O-(2-thiodiphosphate) was used to compete with endogenous GTP in outside-out or inside-out experiments. Pretreatment of dissociated cells with pertussis toxin (0.1 micrograms/ml) blocked muscarinic inhibition of the channel in a time-dependent fashion. These results demonstrate, at the single-channel level, a coupling between muscarinic receptor stimulation and inhibition of KCa in smooth muscle and demonstrate the guanine nucleotide dependence of this coupling.
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PMID:Muscarinic inhibition of single KCa channels in smooth muscle cells by a pertussis-sensitive G protein. 176 21

The circadian rhythm of melatonin output displayed by chick pineal cells in static culture damps rapidly in constant red light (RR). This can be seen in the first cycle following a switch from a cycle of 12 hr white light (L) and 12 hr red light (R) to RR. Melatonin output is higher during the "day" in R than it is in L, but higher that next night (in R) after daytime L than after daytime R. This effect might be due entirely to the entraining effect of L. Alternatively, the higher nocturnal output after daytime L could be related to the acute suppression caused by L; it might be a "rebound" phenomenon. These alternative hypotheses differ in their predictions for the effects of norepinephrine (NE) and pertussis toxin (PT). Previous results dissociated the acute and entraining effects of L: PT blocks the acute effect but not the entraining effect of L. NE mimics the acute effect of L (and is blocked by PT), but not the entraining effect. If L prevents damping entirely by entrainment, then NE should not mimic and PT should not block this same-cycle effect of daytime L on nocturnal melatonin output. However, the present research found that NE did mimic and PT did block this effect, indicating that the ability of L to prevent damping is mediated by a same-cycle "rebound" following L's acute inhibition of melatonin production. Furthermore, NE enhanced the "rebound" effect of daytime L, and cycles substituting NE for L were effective in driving the melatonin rhythm. Lowering extracellular potassium did not induce a "rebound," and adding exogenous melatonin did not prevent one. The difference between nocturnal melatonin synthesis after daytime R and that after daytime L or NE implies regulation of coupling between the output of the circadian pacemaker and melatonin production. These results also suggest a role for NE in regulating and maintaining the expression of the melatonin rhythm.
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PMID:Light and norepinephrine similarly prevent damping of the melatonin rhythm in cultured chick pineal cells: regulation of coupling between the pacemaker and overt rhythms? 177 87

The pathway by which peptide YY inhibits upper gastrointestinal motility is largely unknown and prompted this investigation. Muscle tension and [3H]acetylcholine release studies were performed on isolated muscle strips and slices obtained from the guinea pig stomach. Peptide YY [0.1-1000 nmol/L; concentration of half-maximal effect (EC50), 6 nmol/L] caused concentration-dependent relaxation of longitudinally oriented muscle strips that was unaffected by hexamethonium but was blocked by atropine and tetrodotoxin, suggesting that the peptide inhibited postganglionic cholinergic neurotransmission. In addition, peptide YY (1 mumol/L) reduced by 42% +/- 6% electrically stimulated muscle contractions that were blocked by atropine and tetrodotoxin, providing additional evidence that the peptide inhibits release of acetylcholine. Next, the effect of peptide YY on potassium-evoked release of [3H]acetylcholine and whether the peptide inhibits cyclic adenosine monophosphate-dependent release of acetylcholine were examined. Peptide YY (1 mumol/L) inhibited KCl (35 mmol/L)-evoked release of [3H]acetylcholine by 58% +/- 6%. The inhibitory action of peptide YY was unaffected by antagonists for dopamine-2, alpha-2, and opiate receptors that are known to mediate presynaptic inhibition. In addition, peptide YY reduced half-maximal forskolin and cholera toxin-evoked release of acetylcholine by 45% +/- 6% and 42% +/- 8%, respectively, suggesting that the peptide can inhibit cyclic adenosine monophosphate-dependent release of acetylcholine. This effect of peptide YY was reversed by pertussis toxin which prevents activation of the inhibitory guanine nucleotide binding protein coupled to adenylate cyclase. In summary, peptide YY inhibited basal and stimulated cholinergic neurotransmission in the guinea pig stomach. In addition, peptide YY antagonized cyclic adenosine monophosphate-mediated release of acetylcholine through a pertussis toxin-sensitive mechanism.
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PMID:Mechanism of action of peptide YY to inhibit gastric motility. 184 99

The effects of guanosine 5'-triphosphate (GTP) and GTP-gamma-S, known activators of GTP binding proteins, on proton transport were investigated in endosome-enriched vesicles (endosomes). Endosomes were prepared from rabbit renal cortex following the intravenous injection of FITC-dextran. The rate of intravesicular acidification was determined by measuring changes in fluorescence of FITC-dextran. Both GTP and GTP-gamma-S stimulated significantly the initial rate of proton transport. In contrast, GDP-beta-S, which does not activate GTP binding proteins, inhibited proton transport. The rank order of stimulation was GTP-gamma-S greater than GTP greater than control greater than GDP-beta-S. GTP-gamma-S stimulation of proton transport was also observed under conditions in which chloride entry was eliminated, i.e., 0 mM external chloride concentration in the presence of potassium/valinomycin voltage clamping. GTP-gamma-S did not affect proton leak in endosomes as determined by collapse of H+ ATPase-generated pH gradients. ADP ribosylation by treatment of endosomal membranes with pertussis toxin revealed two substrates corresponding to the 39-41 kD region and comigrating with alpha i subunits. Pretreatment of the membranes with pertussis toxin had no effect on proton transport in the absence of GTP or GTP-gamma-S. However, pretreatment with pertussis toxin blocked the stimulation of proton transport by GTP. In contrast, as reported in other membranes by others previously, pertussis toxin did not prevent the stimulation of proton transport by GTP-gamma-S. These findings, taken together, indicate that GTP binding proteins are present in endosomal membranes derived from renal cortex and that activation of G protein by GTP and GTP-gamma-S stimulates proton transport in a rank order identical to that reported for other transport pathways modulated by Gi proteins. Therefore, these studies suggest that G proteins are capable of stimulating the vacuolar H ATPase of endosomes directly.
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PMID:A potential role for guanine nucleotide-binding protein in the regulation of endosomal proton transport. 185 Jul 57

Previous studies have shown that ATP enhances intracellular calcium concentration and activates potassium channels in Madin Darby canine kidney (MDCK)-cells, thus leading to hyperpolarization of the cell membrane. The present study has been performed to elucidate the intracellular mechanisms involved. To this end, the effects of ATP on the potential difference across the cell membrane (PD), on formation of inositol phosphates, and on intracellular calcium concentration (Cai) have been analyzed in cells without or with pretreatment with pertussis toxin or 12-O-tetradecanoyl phorbol 13-acetate diester (TPA). In untreated cells, ATP leads to a sustained hyperpolarization and an increase of inositol 1,4,5-trisphosphate (IP3), inositol 1,3,4,5-tetrakisphosphate (IP4), and Cai. In the absence of extracellular calcium, the effect of ATP on PD and Cai is only transient. In cells pretreated with pertussis toxin, the effect of ATP on inositol trisphosphate is almost abolished, but ATP still leads to an increase of PD and Cai, which is sustained in the presence, and transient in the absence, of extracellular calcium. In cells pretreated with TPA, the effect of ATP on inositol trisphosphate is reduced and the effect on Cai blunted; but ATP still leads to a hyperpolarization of the cell membrane, which is sustained in the presence, and transient in the absence, of extracellular calcium. The observations indicate that ATP activates phospholipase C by a phorbol ester and pertussis toxin sensitive mechanism. In addition, ATP enhances Cai by pertussis toxin insensitive mechanisms allowing recruitment of calcium from both, extracellular fluid and intracellular stores. Calcium then activates the potassium channels and thus leads to the hyperpolarization of the cell membrane.
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PMID:Cellular mechanisms of ATP-induced hyperpolarization in renal epitheloid MDCK-cells. 190 96

Neuropeptide Y (NPY) is a unique peptide with wide distribution in central and peripheral nervous systems. In the guinea pig, NPY-positive fibers are prominent in the myenteric plexus. To test whether NPY inhibits myenteric plexus acetylcholine (ACh) release and to define mechanisms, a purified preparation of myenteric plexus neurons was derived from the teniae coli of neonatal guinea pigs and maintained in primary culture. Incubation of cultured neurons labeled with [3H]ACh in the presence of NPY (10(-14)-10(-6) M) significantly inhibited basal ACh release (83 +/- 16 to 58 +/- 11% of control). NPY significantly inhibited ACh release stimulated by potassium (55 mM); by adenylate cyclase agonists forskolin (10(-6) M) and cholera toxin (10(-8) M); and by calcitonin gene-related peptide, cholecystokinin octapeptide, and vasoactive intestinal peptide (each 10(-8) M). In each instance, the inhibitory effects of NPY were reversed by preincubation with pertussis toxin. Reversal of inhibitory effects by pertussis toxin suggests that the actions of NPY are mediated via an inhibitory GTP-binding protein.
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PMID:Inhibition of acetylcholine release from guinea pig myenteric neurons by neuropeptide Y: GTP-binding protein mediation. 190 63

Bradykinin triggered intracellular Ca mobilizations and ionic conductance changes were studied in the neuroblastoma x glioma hybrid cell line NG108-15 using Ca-sensitive fluorescent indicator fura-2 under patch pipette whole cell voltage clamp condition. The time course of outward current induced by bradykinin was closely related to the time-course of [Ca2+]i change. Following application of bradykinin, [Ca2+]i increased transiently and then decreased below the basal level before bradykinin application. The inward currents activated by step-depolarization were suppressed after bradykinin application, but the time-course of the suppression did not go in parallel with the [Ca2+]i changes: the suppression started before the [Ca2+]i change emerged and outlasted the phase of [Ca2+]i increase. Both transient type and long-lasting type Ca current were suppressed by bradykinin. [Ca2+]i increase induced by high potassium depolarization was suppressed by bradykinin. Pertussis toxin did not affect the Ca transient nor the suppression of Ca channel induced by bradykinin. Our results suggest that the modifications of ionic channels by bradykinin could be through the other mechanisms than the well established activation of the G-protein leading to the IP3 mechanisms and that the bradykinin receptor might couple with the pertussis toxin-insensitive G protein which regulates the calcium channels.
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PMID:Mobilization of intracellular Ca2+ and suppression of inward currents in a neuronal hybrid cell line triggered by bradykinin. 196 37

The effects of adenosine receptor stimulation on the contractile force of rabbit isolated left atrial preparations in the absence and presence of cAMP-generating and cAMP-independent agonists were investigated. Adenosine and the stable adenosine analogues 5'-(N-ethyl)carboxamido adenosine (NECA) and (-)-N6-phenylisopropyladenosine (R-PIA) produced a concentration-dependent direct negative inotropic effect. Responses to NECA and R-PIA were insensitive to atropine and were shifted to the right by the adenosine receptor antagonist 3-isobutyl-1-methyl xanthine (IBMX). NECA and R-PIA were found to reverse positive inotropic responses of left atria to the beta-adrenoceptor agonist, isoproterenol, but were less effective at reversing positive inotropic responses to the adenylate cyclase activator, forskolin, and were almost ineffective at reversing positive inotropic responses to alpha-adrenoceptor stimulation. Neither NECA nor R-PIA had a significant effect on basal cAMP levels or on cAMP levels elevated by isoproterenol in rabbit left atria. Similarly, R-PIA had no significant effect on basal cAMP levels or isoproterenol-induced increases in cAMP in the presence of adenosine deaminase to remove the influence of endogenous adenosine. Pretreatment of rabbits with 1.75 micrograms/kg pertussis toxin attenuated both the direct negative inotropic response of left atria to NECA and responses to NECA in the presence of isoproterenol and forskolin to a similar extent. Pretreatment of left atrial preparations with the potassium channel antagonist 4-aminopyridine resulted in a dose dependent attenuation of responses to NECA alone and in the presence of isoproterenol and forskolin. These data suggest that adenosine receptors in rabbit left atria are not coupled to adenylate cyclase.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The interaction of adenosine analogues with cAMP-generating and cAMP-independent positive inotropic agents in rabbit left atrium. 196 30

Despite their widespread occurrence in the central nervous system, interactions between co-localized transmitters and their receptors remain poorly understood. Noradrenergic neurons of the nucleus locus coeruleus contain the peptide co-transmitter neuropeptide Y (refs 1,2). In locus coeruleus cells, stimulation of alpha2-adrenoceptors 3,4 or opioid mu-receptors 5,6 increases a potassium conductance and thereby leads to hyperpolarization and inhibition of spontaneous firing. Coupling between these receptors and the inward rectifying K+ channels involves a pertussis toxin-sensitive GTP-binding protein (Gi or Go)7. Here we investigate whether the neuropeptide Y and alpha2-receptors of locus coeruleus neurons interact with one another. When administered alone, neuropeptide Y reduces the discharge of action potentials, probably by increasing the permeability of the membrane to potassium ions through the activation of a G protein; this effect is reduced in the presence of alpha2-adrenoceptor antagonists. Moreover, the peptide selectively increases the hyperpolarizing effect of alpha2-agonists, but does not enhance responses to opioid mu-agonists. We suggest that noradrenaline and its co-transmitter neuropeptide Y stimulate separate receptors, which influence each other in a specific way.
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PMID:Interaction between neuropeptide Y and noradrenaline on central catecholamine neurons. 196 29

Agonists at alpha 2-adrenoceptors, delta-opioid receptors, and somatostatin receptors were applied to dissociated guinea pig submucous plexus neurons; whole-cell recordings of membrane current showed that they increased the membrane potassium conductance. The conductance affected showed inward rectification, being described by Gag(max)/[1 + exp((V - V0.5)/k)] where V0.5 was about -65 mV and Gag(max) was about 10 nS. The agonists were ineffective when the potassium conductance of the neurons had first been increased by intracellular dialysis with purified guanosine 5'-triphosphate (GTP)-binding proteins (Gi or Go). Agonist actions were prevented by pertussis toxin, applied intracellularly (10-100 ng/ml for several minutes) or extracellularly 1-10 micrograms/ml for 1 hr); in the latter case, the agonist responses were reconstituted by intracellular dialysis with GTP-binding proteins.
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PMID:Potassium conductance increased by noradrenaline, opioids, somatostatin, and G-proteins: whole-cell recording from guinea pig submucous neurons. 197 Jun 5


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