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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acetylcholine is known to stimulate the secretion of growth hormone and prolactin and the efflux of 86Rb from bovine anterior pituitary cells: dopamine prevents the stimulation of 86Rb efflux and of prolactin but not growth hormone secretion. The sensitivity of these responses to pertussis toxin has been determined. Treatment of bovine anterior pituitary cells in primary culture with pertussis toxin (18 h, 100 ng/ml) did not modify the stimulation of prolactin secretion by acetylcholine, but prevented its inhibition by dopamine. In lactotrophs, dopamine but not acetylcholine receptors are therefore coupled to secretion through a pertussis toxin substrate. The stimulation of 86Rb efflux by acetylcholine was also unaffected by pertussis toxin and, again, its inhibition by dopamine was prevented. Treatment of the cells with pertussis toxin enhanced the secretion of growth hormone in response to acetylcholine. Nitrendepine (1 mumol/l) prevented the cholinergic stimulation of growth hormone but not prolactin secretion from these cells. Acetylcholine increased the cytoplasmic calcium concentration and this rise was enhanced by treatment of the cells with pertussis toxin. Nitrendepine partially inhibited the rise in calcium caused by acetylcholine, and prevented the enhancement of the rise following pertussis toxin treatment. Cholinergic stimulation of growth hormone therefore depends on calcium entry through nitrendepine-sensitive channels, whereas stimulation of prolactin secretion does not, and in somatotrophs a pertussis toxin substrate may limit calcium entry through these channels. These different sensitivities of somatotrophs and lactotrophs to pertussis toxin and nitrendepine may reflect differences in the properties of the predominant calcium currents in the two cell types.
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PMID:Modification by pertussis toxin of the responses of bovine anterior pituitary cells to acetylcholine and dopamine: effects on hormone secretion and 86Rb efflux. 335 28

1. Whole-cell patch-clamp technique was used to study the beta-adrenergic and cholinergic regulation of the inwardly rectifying K+ conductance (gK1) in isolated guinea-pig ventricular myocytes. 2. In Cl(-)-free solutions or in the presence of 9-anthracenecarboxylic acid or Co2+, bath-applied isoprenaline (Iso) partially inhibited the steady-state whole-cell conductance (gss) calculated from the steady-state current (Iss)-voltage (Iss-V) curve at membrane voltages (Vm) negative to the equilibrium potential for potassium (EK). Iss was also inhibited at Vm positive to EK when the extracellular [K+] was 20 mM. The Iso-sensitive component of gss exhibited the characteristics of the inwardly rectifying K+ conductance (gK1). 3. The Iso-induced inhibition of gK1 was reversible, concentration dependent, blocked by propranolol, mimicked by both forskolin and dibutyryl cAMP, and prevented by including a cAMP-dependent protein kinase (PKA) inhibitor in the pipette solution. These findings suggest that PKA mediates the Iso-induced inhibition of gK1. 4. The apparent dissociation constant (KD) for the concentration dependence of Iso-induced inhibition was 0.035 microM and the Hill coefficient was approximately 1.0. A maximal Iso concentration (1 microM) inhibited gK1 by 40 +/- 4.1% (mean +/- S.E.M.; n = 13). 5. Bath application of acetylcholine (ACh, 0.1 microM or more) antagonized the Iso-induced (1 microM) inhibition of gK1; [ACh] > 1.0 microM antagonized 88 +/- 2.1% (n = 10) of the inhibition. ACh increased the KD for Iso to inhibit Iso-sensitive gK1 and also reduced the maximal Iso-induced inhibition. 6. ACh-induced antagonism could be abolished by pre-incubating myocytes with pertussis toxin (PTX), suggesting that a muscarinic receptor-coupled, PTX-sensitive G protein, Gi, is involved. 7. ACh (10 microM) also antagonized approximately 70% of the dibutyryl cyclic AMP (1 mM)-induced inhibition of gK1 (n = 3), suggesting that the ACh-induced antagonism involves more than simply inhibiting the Iso-mediated activation of adenylyl cyclase via the activated Gi. 8. Intracellularly applied okadaic acid (OkA, 1 microM) did not alter gK1 (control = 134 +/- 5.1 nS vs. OkA = 136 +/- 6.1 nS), but the Iso-induced decrease in gK1 was less (P < 0.001) with OkA present (42.1 +/- 2.4 nS, n = 5) than when absent (54.0 +/- 2.2 nS, n = 10). However, ACh (10 microM) failed to antagonize Iso-induced inhibition with OkA present, suggesting involvement of a protein phosphatase.
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PMID:beta-adrenergic and cholinergic modulation of the inwardly rectifying K+ current in guinea-pig ventricular myocytes. 747 26

The cellular mechanism of autonomic regulation of the catecholamine-induced chloride current (ICl) was investigated by recording the whole-cell current in isolated guinea-pig ventricular cells. The beta-adrenergic and related stimulations such as adrenaline, isoprenaline, forskolin, or internal application of cyclic AMP (cAMP), induced the ICl. Acetylcholine (ACh) depressed the responses of ICl induced by the beta-adrenergic stimulation or forskolin, which was followed by a transient overshoot of the ICl response upon washing out ACh. ACh failed to interfere with ICl induced by cAMP, and the pretreatment of myocytes with pertussis toxin (PTX) abolished the inhibitory effect of acetylcholine. Intracellular application of cGMP, which levels are known to be elevated by the muscarinic stimulation, enhanced ICl activated by submaximal doses of isoprenaline. In the absence of agonists, cGMP failed to induce ICl. Thus, the antagonistic interaction between the beta-adrenergic stimulation and the muscarinic stimulation is at the membrane level, most probably via PTX-sensitive GTP-binding proteins. cGMP might contribute to the post-ACh rebound phenomenon by facilitating the beta-stimulation.
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PMID:Autonomic regulation of cardiac chloride current. 753 7

In bovine adrenal zona fasciculata (AZF) cells, angiotensin II (AII) may stimulate depolarization-dependent Ca2+ entry and cortisol secretion through inhibition of a novel potassium channel (IAC), which appears to set the resting potential of these cells. Aspects of the signaling pathway, which couples AII receptors to membrane depolarization and secretion, were characterized in patch clamp and membrane potential recordings and in secretion studies. AII-mediated inhibition of IAC, membrane depolarization, and cortisol secretion were all blocked by the AII type I (AT1) receptor antagonist losartan. These responses were unaffected by the AT2 antagonist PD123319. Inhibition of IAC by AII was prevented by intracellular application of guanosine 5'-O-2-(thio)-diphosphate but was not affected by pre-incubation of cells with pertussis toxin. Although mediated through an AT1 receptor, several lines of evidence indicated that AII inhibition of IAC occurred through an unusual phospholipase C (PLC)-independent pathway. Acetylcholine, which activates PLC in AZF cells, did not inhibit IAC. Neither the PLC antagonist neomycin nor PLC-generated second messengers prevented IAC expression or mimicked the inhibition of this current by AII. IAC expression and inhibition by AII were insensitive to variations in intracellular or extracellular Ca2+ concentration. AII-mediated inhibition of IAC was markedly reduced by the non-hydrolyzable ATP analog adenosine 5'-(beta, gamma-imino)triphosphate and by the non-selective protein kinase inhibitor staurosporine. The protein phosphatase antagonist okadaic acid reversibly inhibited IAC in whole cell recordings. These findings indicate that AII-stimulated effects on IAC current, membrane voltage, and cortisol secretion are linked through a common AT1 receptor. Inhibition of IAC in AZF cells appears to occur through a novel signaling pathway, which may include a losartan-sensitive AT1 receptor coupled through a pertussis-insensitive G protein to a staurosporine-sensitive protein kinase. Apparently, the mechanism linking AT1 receptors to IAC inhibition and Ca2+ influx in adrenocortical cells is separate from that involving inositol trisphosphate-stimulated Ca2+ release from intracellular stores. AII-stimulated cortisol secretion may occur through distinct parallel signaling pathways.
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PMID:Losartan-sensitive AII receptors linked to depolarization-dependent cortisol secretion through a novel signaling pathway. 767 18

The effect of platelet-activating factor (PAF) on neurotransmitter release from rat brain slices prelabeled with [3H]acetylcholine ([3H]ACh), [3H]norepinephrine ([3H]NE), or [3H]serotonin ([3H]5-HT) was studied. PAF inhibited K+ depolarization-induced [3H]ACh release in slices of brain cortex and hippocampus by up to 59% at 10 nM but did not inhibit [3H]ACh release in striatal slices. PAF did not affect 5-HT or NE release from cortical brain slices. The inhibition of K(+)-evoked [3H]ACh release induced by PAF was prevented by pretreating tissues with several structurally different PAF receptor antagonists. The effect of PAF was reversible and was not affected by pretreating brain slices with tetrodotoxin. PAF-induced inhibition of [3H]ACh release was blocked 90 +/- 3 and 86 +/- 2% by pertussis toxin and by anti-G alpha i1/2 antiserum incorporated into cortical synaptosomes, respectively. The results suggest that PAF inhibits depolarization-induced ACh release in brain slices via a G alpha i1/2 protein-mediated action and that PAF may serve as a neuromodulator of brain cholinergic system.
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PMID:Platelet-activating factor: diminished acetylcholine release from rat brain slices is mediated by a Gi protein. 793 26

Elevation of adenosine 3',5'-cyclic monophosphate (cAMP) levels in Necturus gallbladder (NGB) epithelium activates an apical membrane Cl- conductance and decreases transepithelial fluid transport (Jv). Acetylcholine (ACh), which had no effects on Jv by itself, antagonized the electrophysiological effects of forskolin (FSK) and theophylline and the decrease in Jv produced by FSK. By itself, ACh had no effects on basal cAMP levels but antagonized the increases in cAMP induced by FSK and theophylline. ACh had no effect on phosphodiesterase activity and prevented both the electrophysiological response and the elevation in cAMP by theophylline. In conclusion, the effect of ACh is mediated by inhibition of adenylate cyclase. A pertussis toxin (PTX)-sensitive G protein may mediate inhibition of adenylate cyclase because pretreatment with PTX prevented the reversal of the electrophysiological effects of FSK by ACh, and PTX catalyzed the ribosylation of cell membranes from NGB epithelium. ACh could have a physiological role in modulating the effects of secretagogues that act via elevation of cAMP levels.
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PMID:Muscarinic stimulation of gallbladder epithelium. III. Antagonism of cAMP-mediated effects. 797 83

Following postsynaptic activation of a pyramidal cell, the degree of GABAergic synaptic inhibition that the cell receives is reduced dramatically for many seconds. Previously, we found that induction of depolarization-induced suppression of inhibition (DSI) required post-synaptic increases in intracellular [Ca2+], but absence of a decrease in responsiveness to iontophoretically applied GABA left the mechanism of DSI expression uncertain. We investigated DSI with whole-cell voltage-clamp recordings in rat hippocampal slices. Bath-applied carbachol was ordinarily used to increase the spontaneous action potential-induced IPSCs (sIPSCs) and enhance detectability of DSI; synaptically released ACh has the same effects. TTX-sensitive sIPSCs are markedly reduced by DSI, whereas TTX-insensitive miniature IPSC amplitudes do not change, suggesting that DSI represents a retrograde influence on presynaptic GABA release. A lag (approximately 1 s) prior to maximal DSI and prevention of DSI by pertussis toxin pointed to a G protein-linked second messenger that may be presynaptic, since perturbation of postsynaptic G protein function did not alter DSI.
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PMID:Depolarization-induced suppression of GABAergic inhibition in rat hippocampal pyramidal cells: G protein involvement in a presynaptic mechanism. 799 36

1. 5-Hydroxytryptamine (5-HT) has been shown to induce contraction of tracheal smooth muscle. However, the mechanisms of action of 5-HT are not known. We therefore investigated the effects of 5-HT on phospholipase C (PLC)-mediated phosphoinositide (PI) hydrolysis and its regulation in canine cultured tracheal smooth muscle cells (TSMCs) labelled with [3H]-inositol. 5-HT-induced inositol phosphates (IPs) accumulation was time- and dose-dependent with a half-maximal response (EC50) and a maximal response at 0.38 +/- 0.05 and 10 microM, respectively. 2. Ketanserin and mianserin (10 and 100 nM), 5-HT2 receptor antagonists, were equipotent in blocking the 5-HT-induced IPs accumulation with pKB values of 8.46 and 8.21, respectively. In contrast, the dose-response curves of 5-HT-induced IPs accumulation were not shifted until the concentrations of NAN-190 and metoclopramide (5-HT1A and 5-HT3 receptor antagonists, respectively) were increased up to 10 microM. 3. Pretreatment of TSMCs with pertussis toxin or cholera toxin did not inhibit the 5-HT-induced IPs accumulation, but partially inhibited the AlF(4-)-induced IPs response. 4. Stimulation of IPs accumulation by 5-HT required the presence of external Ca2+ and was blocked by EGTA. The addition of Ca2+ (3-620 nM) to digitonin-permeabilized TSMCs directly stimulated IPs accumulation. A further Ca(2+)-dependent increase in IPs accumulation was obtained by inclusion of either guanosine 5'-O-(3-thiotriphoshate) (GTP gamma S) or 5-HT. The combination of GTP gamma S and 5-HT elicited an additive effect on IPs accumulation. 5. Treatment with phorbol 12-myristate 13-acetate (PMA, 1 microM, 30 min) abolished the 5-HT-induced IPs accumulation. The concentrations of PMA that gave a half-maximal and maximal inhibition of 5-HT-induced IPs accumulation were 2.2 +/- 0.4 nM and 1 microM, n = 3, respectively. The protein kinase C (PKC) activator, 4 alpha-phorbol 12,13-didecanoate, at 1 microM, did not influence this response. The inhibitory effect of PMA was reversed by staurosporine, a PKC inhibitor, suggesting that the inhibitory effect of PMA is mediated through the activation of PKC. 6. The site of this inhibition was further investigated by examining the effect of PMA on AlF(4-)-induced IPs accumulation in canine TSMCs. AlF(4-)-stimulated IPs accumulation was inhibited by PMA treatment, suggesting that the effect of PMA is distal to the 5-HT receptor. 7. Acetylcholine-induced IPs accumulation was completely inhibited by atropine, but not affected by ketanserin or mianserin, suggesting that 5-HT-induced IPs accumulation is not due to release of acetylcholine.8. These results demonstrate that 5-HT directly stimulates PLC-mediated PI hydrolysis via a pertussis toxin- and cholera toxin-insensitive GTP binding protein in canine TSMCs and that this coupling process is negatively regulated by PKC. 5-HT2 receptors may be predominantly mediating IPs accumulation and presumably IP-induced Ca2+ release may function as the transducing mechanism for 5-HT stimulated contraction of tracheal smooth muscle.
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PMID:5-Hydroxytryptamine receptor-mediated phosphoinositide hydrolysis in canine cultured tracheal smooth muscle cells. 801 56

Acetylcholine released during parasympathetic stimulation of the vagal nerve slows the heart rate through the activation of muscarinic receptors and subsequent opening of an inwardly rectifying potassium channel. The activation of these muscarinic potassium channels is mediated by a pertussis toxin-sensitive heterotrimeric GTP-binding protein (G protein). It has not been resolved whether exogenously applied G alpha or G beta gamma, or both, activate the channel. Using a heterologous expression system, we have tested the ability of different G protein subunits to activate the cloned muscarinic potassium channel, GIRK1. We report here that coexpression of GIRK1 with G beta gamma but not G alpha beta gamma in Xenopus oocytes results in channel activity that persists in the absence of cytoplasmic GTP. This activity is reduced by fusion proteins of the beta-adrenergic receptor kinase and of recombinant G alpha i-GDP, both of which are known to interact with G beta gamma. Moreover, application of recombinant G beta gamma, but not G alpha i-GTP-gamma S, activates GIRK1 channels. Thus G beta gamma appears to be sufficient for the activation of GIRK1 muscarinic potassium channels.
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PMID:Activation of the cloned muscarinic potassium channel by G protein beta gamma subunits. 802 83

Muscarinic acetylcholine receptor (mAChR) subtype (m1-m4)-specific cDNAs were transfected into NL308 neuroblastoma-fibroblast hybrid cells and clones expressing each of the individual mAChR subtypes m1, m2, m3 and m4 obtained. Acetylcholine increased phosphoinositide (PI) turnover in m1- and m3-transformed cells, but did not produce detectable changes in m2- and m4-transformed cells. In cells expressing m1 and m3 subtypes, ACh produced an initial outward K+ current, followed by a cationic current. In cells expressing m2 and m4 receptors, only the initial K+ current was detected. The outward currents were associated with a rise in intracellular Ca2+ as measured with Fura-2 or Indo-1, and were inhibited by chelating intracellular Ca2+ with external BAPTA-AM, or by external charybdotoxin or Ba2+: hence they were attributed to the activation of a Ca(2+)-dependent K+ current. However, the outward current produced in m2- and m4-transformed cells was blocked by pretreatment with 5 ng ml-1 Pertussis toxin (PTX), whereas that in m1- and m3-transformed cells was not. These results suggest that m2- and m4-receptors in transformed NL308 cells coupled to PTX-sensitive G-protein which is capable of mobilizing intracellular Ca2+ and activate IK(Ca), whereas m1 and m3 receptors activate a similar process through a different, PTX-insensitive G-protein.
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PMID:Coupling of m2 and m4 muscarinic acetylcholine receptor subtypes to Ca(2+)-dependent K+ channels in transformed NL308 neuroblastoma x fibroblast hybrid cells. 809 28


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