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)

Intracellular recording from hippocampal CA1 pyramidal cells was used to characterize the pharmacological properties of muscarinic responses. Results obtained with the M1 antagonist pirenzepine and the M2 antagonist gallamine suggest that an M1 muscarinic receptor is involved in the muscarinic-induced membrane depolarization and blockade of the afterhyperpolarization (AHP). On the other hand, an M2 receptor may be involved in the cholinergic depression of the EPSP and the blockade of the potassium current termed the M-current. Pretreatment of hippocampi with pertussis toxin did not prevent any of the muscarinic responses suggesting that a pertussis toxin-sensitive G-protein is not involved. The M-current, in contrast to the other muscarinic actions, was unaffected by muscarinic agonists which are weak at increasing phosphoinositide (PI) turnover and actually blocked the action of full agonists. This finding suggests that stimulation of PI turnover may be involved in the blockade of the M-current. Although activation of protein kinase C with phorbol esters has little effect on the M-current, intracellular application of inositol trisphosphate did reduce the M-current. We were unable to establish any clear relationship between biochemical effector systems and the muscarinic receptor subtypes.
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PMID:Pharmacological characterization of muscarinic responses in rat hippocampal pyramidal cells. 253 6

The present study examines the influence of potassium and sodium ions on guanine nucleotide regulation of adenylate cyclase in various brain regions, including the locus coeruleus (LC), dorsal raphe (DR), ventral tegmentum (VT), hippocampus (HP), frontal cortex (FC), substantia nigra (SN), neostriatum (NS) and cerebellum (CB). Guanine nucleotide regulation of adenylate cyclase was highest in the LC, DR and VT and lowest in NS and CB. Sodium and potassium ions were found to stimulate basal or GTP-activated adenylate cyclase in NS and SN, whereas the cations were found to specifically inhibit guanine nucleotide-stimulated enzyme activity in all other brain regions with the exception of CB, where there was no effect. With regard to stimulation of adenylate cyclase, lithium was more potent than sodium which was more potent than potassium in SN and NS. With regard to inhibition of the enzyme, potassium was equipotent to lithium which was greater than sodium in the other brain regions examined. Both stimulatory and inhibitory effects of cations in the different regions were significant (P less than 0.05) at 30 mM and were maximal at 90-120 mM. Sodium ion inhibition of GTP-stimulated adenylate cyclase in LC and DR was partially blocked by pertussis toxin treatment, whereas cation stimulation in NS was not affected by the toxin. The results demonstrate marked region-specific effects of sodium and potassium on adenylate cyclase, which could occur at either G-proteins or the catalytic unit of the enzyme. The possibility that ion fluxes alter G-protein function is discussed.
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PMID:Sodium and potassium regulation of guanine nucleotide-stimulated adenylate cyclase in brain. 254 4

The GABA application evoked fast picrotoxin-sensitive depolarization as well as slow depolarization with decreasing membrane conductivity and hyperpolarization with increasing membrane conductivity in the neurons of the rat dorsal root ganglion. The slow picrotoxin-resistant responses to GABA were initiated with phenibut. The phenibut effects were modulated by cAMP concentration and inhibited by the pertussis toxin. The reversal potential of the phenibut effects was equal to the potassium equilibrium one. The phenibut effects were reduced by increasing K+ and Ca+ extracellular concentration, and enhanced in presence of trifluoroperazine.
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PMID:[Analysis of the nature of responses of neurons of rat spinal ganglia evoked by the activation of GABA-B receptors]. 254 67

gamma-Aminobutyric acidB (GABAB) receptor recognition sites that inhibit cyclic AMP formation, open potassium channels, and close calcium channels are coupled to these effector systems by guanine nucleotide binding proteins (G proteins). These G proteins are ADP-ribosylated by islet-activating protein (IAP), also known as pertussis toxin. This process prevents receptor coupling to these G proteins. In slices of cerebral cortex and hippocampus from rat, stimulation of GABAB receptors with baclofen, a receptor agonist, also potentiates the accumulation of cyclic AMP stimulated by beta-adrenergic agonists. It was unknown whether those GABAB receptors that potentiate the beta-adrenergic response were also sensitive to IAP. IAP was injected intracerebroventricularly into rats to ADP-ribosylate IAP-sensitive G proteins. Four days after the IAP injection, 38% and 52% of these G proteins from cerebral cortex and hippocampus, respectively, were ADP-ribosylated by the IAP injection. In slices of both structures prepared from IAP-treated rats, the GABAB receptor-mediated potentiation of the beta-adrenergic receptor response was attenuated. Thus, many GABAB receptor-mediated responses are coupled to IAP-sensitive G proteins.
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PMID:Islet-activating protein inhibits the beta-adrenergic receptor facilitation elicited by gamma-aminobutyric acidB receptors. 254

Capsaicin, which induces fluxes of sodium, calcium, and potassium ions in a subset of both neonatal and adult rat dorsal root ganglion neurones, increased cyclic GMP (cGMP) levels by a factor of 20 (EC50 0.07 microM) to 10-20 pmol cGMP/mg protein in these cells. Cyclic AMP (cAMP) levels were unaffected. Nonneuronal cells derived from rat ganglia, and both neurones and nonneuronal cells from chick were unresponsive to capsaicin. Capsaicin-induced cGMP elevation in rat dorsal root ganglion (DRG) neurones was unaffected by pertussis toxin, lowered by compounds that block voltage-sensitive calcium channels, and was abolished by the removal of extracellular calcium. Calcium, guanidine, and rubidium fluxes were unaffected by treatment of DRG cells with sodium nitroprusside or dibutyryl cGMP. The cGMP response to capsaicin is thus a function of capsaicin-evoked calcium uptake through voltage-sensitive calcium channels. Elevated cGMP levels do not, however, contribute to capsaicin-evoked ion fluxes or to their desensitisation.
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PMID:Capsaicin-induced ion fluxes increase cyclic GMP but not cyclic AMP levels in rat sensory neurones in culture. 254 99

The concept of multifactorial pituitary control is now well established. As in other cell systems, integration of complex messages involves dynamic interactions of receptors and coupling mechanisms. Regulation of adenohypophyseal secretions has been shown to involve cyclic AMP production, the modulation of phosphatidylinositol phosphate breakdown and Ca2+ mobilization. Dopamine, somatostatin and angiotensin II receptors are negatively coupled to adenylate cyclase in anterior pituitary cells. In the case of angiotensin, this effect on adenylate cyclase appears paradoxical since the peptide markedly stimulates prolactin secretion. In fact, angiotensin II also markedly stimulates inositol phosphate production and this effect could account for the stimulated hormone secretion. In addition, dopamine could inhibit inositol phosphate production stimulated by angiotensin II and thyrotropin-releasing hormone. Dopamine and somatostatin also directly modulate voltage-dependent calcium channels, perhaps through a direct coupling with potassium channels. On the other hand, steroids modulate the sensitivity of adenohypophyseal cells to neurohormones by different mechanisms. In the case of somatostatin, it increases the number of specific binding sites, while in the case of dopamine estradiol affects the transduction mechanisms of D2 dopamine receptors. In conclusion, dopamine and somatostatin receptors appear coupled to various transduction mechanisms through pertussis-sensitive G proteins in anterior pituitary cells.
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PMID:Multiple transduction mechanisms of dopamine, somatostatin and angiotensin II receptors in anterior pituitary cells. 256 74

Intracellular recordings from intact pituitary melanotrophs show that, in the same cell, inhibitory postsynaptic potentials resulting from either pituitary stalk stimulation or exogenous dopamine are abolished by D2 receptor antagonists, display identical conductance changes, are reversed in polarity at the same membrane potential and are sensitive to pertussis toxin pretreatment. The reversal potential of the inhibitory postsynaptic potential shows a 65 mV shift with a 10-fold change in external potassium concentration, which is close to that predicted by the Nernst equation. We conclude that activation of this synapse releases dopamine which acts on a D2 receptor to increase potassium conductance via a G-protein-mediated mechanism. This is the first characterization of an inhibitory dopaminergic synapse in the mammalian nervous system.
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PMID:A dopaminergic inhibitory postsynaptic potential mediated by an increased potassium conductance. 259 96

We have investigated the action of pertussis toxin on a range of receptor-mediated responses of the rat superior cervical ganglion in vitro. The ganglia were treated with pertussis toxin for 24 h at 37 degrees C using an in vitro method. Appropriate controls were also carried out. Pertussis toxin (1 microgram/ml) reduced ganglionic hyperpolarisations mediated by adenosine, alpha 2, 5-HT1A, M2 and GABAB receptors. The GABAB-mediated hyperpolarisation of this preparation, evoked by baclofen and GABA in a bicuculline-resistant manner, has not previously been reported. Pertussis toxin did not reduce ganglionic depolarisations evoked by potassium chloride and 5-HT3, GABAA and nicotinic receptors. Depolarisations to muscarine and noradrenaline, probably mediated by M1 and beta-receptors, also appeared to be resistant to pertussis toxin. The similar sensitivity of the various ganglionic hyperpolarisations to pertussis toxin indicates that they may all be mediated by similar G-proteins.
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PMID:Pertussis toxin sensitivity of drug-induced potentials on the rat superior cervical ganglion. 272 73

The membrane potential and conductance alterations of rat dorsal root ganglion neurons evoked by serotonin applied in bath or from a micropipette under pressure have been studied by intracellular technique. Serotonin application evoked depolarization with a decrease in membrane conductance and hyperpolarization with an increase in its conductance. A part of depolarization responses mediated by 5-HT2 receptor activation were independent of intracellular AMP concentration and associated with blockade of M-current channels. The other part of depolarizing and all hyperpolarizing responses mediated by 5-HT1A receptor activation were depressed by pertussis toxin and considerably modulated by intracellular AMP alterations. These responses were shown to be associated with disturbances in the function of AMP-dependent potassium ionic channels.
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PMID:[Metabolic and ionic dependence of neuronal responses evoked by serotonin in the rat sensory ganglia]. 272 90

Neurons in hippocampal and striatal cell cultures respond to adenosine with an inhibitory potassium current. This response disappears during whole-cell patch-clamp recording in which the cell is filled with minimal saline. We have found that this loss of sensitivity to adenosine can be prevented by including 100 microM GTP in the patch electrode filling solution. GDP is less effective than GTP in supporting the adenosine response, while GMP has little, if any, effect. Treatments known to inhibit GTP-binding proteins (G-proteins) block the adenosine-activated potassium current: The adenosine response is inhibited by including poorly metabolized analogs of guanine nucleotides along with GTP in the recording electrode. Diphosphate and triphosphate analogs appear to achieve this effect through different mechanisms. The adenosine response is also blocked by incubating cultures in islet-activating protein (pertussis toxin), an inhibitor of a class of G-protein. Thus, our data implicate a G-protein in the activation of a potassium current by adenosine. Intracellular ATP can increase the effectiveness of GMP, GDP, or low concentrations of GTP, suggesting that even during internal dialysis, neurons can maintain GTP levels through phosphotransferase reactions. Intracellular ATP also appears to suppress an outward current that is different from the adenosine-activated current. Raising intracellular cAMP levels either with bath-applied forskolin or by including a cAMP analog in the recording electrode did not alter the adenosine response. These results indicate that a G-protein is involved in the coupling between the adenosine receptor and a potassium channel, and that this coupling is not mediated by cAMP.
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PMID:Dependence of an adenosine-activated potassium current on a GTP-binding protein in mammalian central neurons. 282 65


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