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)

Corticotropin-releasing factor (CRF) has been shown to attenuate vascular leakage in injured skin, mucous membrane, muscle, and brain. Calcium is thought to play an important role in many of the physiological responses to CRF, but there has been little characterization of how calcium is involved in process by which CRF protects damaged tissues. The goal of this study was to characterize changes in cytosolic free calcium concentrations ([Ca2+]i) in human epidermoid A-431 cells exposed to human/rat-CRF and to investigate the mechanisms by which these changes occur. The resting [Ca2+]i in normal cells at 37 degrees C was 66 +/- 4 nM (n = 32). When cells were treated with CRF, [Ca2+]i increased immediately. The increase depended on CRF concentration, with a median effective concentration of 11 pM. This increase in [Ca2+]i depended on external Ca2+ but not Na+, Mg2+, or K+. La3+ (10 microM) and Co2+ (10 microM) inhibited the CRF-induced [Ca2+]i increase, whereas verapamil and nifedipine tested at concentrations up to 1 mM did not. alpha-Helical CRF-(9-41), a synthetic CRF receptor antagonist, and pertussis toxin blocked the increase in [Ca2+]i induced by CRF, which suggests that the entry of extracellular Ca2+ is mediated by receptor-operated Ca2+ channels coupled with pertussis toxin-sensitive G proteins. Although 420 pM CRF stimulated an immediate increase in [Ca2+]i, inositol trisphosphate and cellular cAMP levels did not change within 1 min either in the presence or absence of external Ca2+.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Corticotropin-releasing factor increases [Ca2+]i via receptor-mediated Ca2+ channels in human epidermoid A-431 cells. 805 Apr 74

To study the cellular basis for FSH-stimulated dose-dependent graded increases in intracellular Ca2+ concentrations in populations of Sertoli cells, we investigated the effects of FSH on free Ca2+ ion concentrations ([Ca2+]i) in individual rat Sertoli cells using the Ca(2+)-sensitive dye fura-2/AM and digital fluorescent videomicroscopy. Ovine or rat FSH elicited a hormone-specific rise in [Ca2+]i within 20-140 sec, with a peak level 2.7 +/- 0.9-fold greater than the basal value (mean +/- SEM; n = 8) lasting for 4-16 min. The amplitude and kinetics of the FSH-induced [Ca2+]i signal were not dose dependent. Instead, increasing doses of FSH recruited a higher percentage of responding cells. Chelation of extracellular Ca2+ or cotreatment with verapamil or cobalt abolished FSH-induced [Ca2+]i increases. Furthermore, in the presence of extracellular Mn2+, direct evidence for FSH-mediated Ca2+ influx was obtained from the quench of fura-2 fluorescence. Induced Ca2+ increases were mimicked by forskolin or protein kinase-A type I activators [8-(6-amino-hexyl)amino-cAMP and N6-benzoyl-cAMP (N6B)]. However, the cAMP analogs, 8-bromo-cAMP, N6,2'-O-dibutyryl cAMP, or protein kinase-A type II activators (8-thiomethyl-cAMP and N6B), induced [Ca2+]i increases even in the absence of extracellular Ca2+, and the time course of the [Ca2+]i rise induced by cAMP analogs was more rapid than that induced by FSH. Similarly, the uninhibited rise in [Ca2+]i induced by FSH in pertussis toxin-pretreated Sertoli cells suggests that PT-sensitive G-proteins are not involved in the action of FSH on [Ca2+]i. In summary, we demonstrate that FSH evokes sustained [Ca2+]i increases in single Sertoli cells in a nongraded fashion and recruits increasing numbers of responding cells in a dose-dependent fashion. We also provide explicit evidence that FSH induces Ca2+ influx. Mimicry of the FSH-induced [Ca2+]i rise by certain cAMP analogs [8-(6-amino-hexyl)amino-cAMP and N6B; protein kinase-A type I activator] or forskolin suggests that Ca2+ may be part of a dual pathway of cAMP-initiated intracellular signaling.
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PMID:Cellular basis for follicle-stimulating hormone-stimulated calcium signaling in single rat Sertoli cells: possible dissociation from effects of adenosine 3',5'-monophosphate. 813 59

The mechanism by which complement fragment C5a elevates intracellular Ca2+ ([Ca2+]i) levels in two cell types, a monocytic cell line, U937, and neutrophils, has been investigated by the use of fluorometric and radiometric techniques. In U937 cells the influx of extracellular Ca2+ can be distinguished from the release of intracellular Ca2+ stores in terms of dose-responsiveness to C5a and sensitivity to pertussis-toxin poisoning. This suggests that the mechanism of Ca2+ influx in these cells is at least partially independent of both the production of inositol phosphates and elevation of internal Ca2+ concentration. The C5a-stimulated influx of 45Ca2+ into U937 cells is inhibited by a series of metal ions (Zn2+ > Co2+ > Mn2+ > Sr2+ approximately equal to Ni2+ > La3+). The stimulated influx of Ca2+ into neutrophils is inhibited differently (Ni2 >> Co2+ > Zn2+ approximately equal to La3+ > Mn2+ approximately equal to Sr2+), is less sensitive to C5a and both the influx of extracellular Ca2+ and the release of intracellular stores are equally sensitive to pertussis toxin treatment. Taken together these results indicate that [Ca2+]i is controlled in U937 monocytes by mechanisms distinct from those which appear to operate in other myeloid cells, such as neutrophils, stimulated with C5a and formylpeptide.
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PMID:Characterization of a complement-fragment-C5a-stimulated calcium-influx mechanism in U937 monocytic cells. 824 Feb 77

Two isoforms of the D2 dopamine receptor exist, termed D2 short (D2s) and D2 long, which differ by the presence or absence of 29 amino acids. To examine the possible coupling of the D2s isoform to voltage-dependent K+ current, NG108-15 cells that were transfected with and stably express this isoform were studied using whole-cell patch-clamp techniques. In transfected, but not untransfected, cells dopamine and quinpirole (QUIN) reduced the normally observed peak outward K+ current, and this effect was abolished by the D2 antagonist sulpiride but not by the alpha 2-adrenergic receptor antagonist idazoxan or the D1 antagonist (R)-(+)-SCH-23380. The D1 receptor agonist SKF 38393 had no effect. QUIN-induced inhibition of K+ current was prevented by loading the cells with the Ca(2+)-chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid, suggesting a critical role for intracellular Ca2+ mobilization. In contrast, reduction of the concentration of extracellular Ca2+ and inclusion of the Ca2+ channel blocker cobalt did not modify the reduction of K+ current produced by stimulation of D2s receptors. A critical role for intracellular calcium mobilization in the observed effects was further supported by the observation that increases in cytosolic Ca2+ produced by thapsigargin mimicked the effect of QUIN, whereas intracellular ryanodine, which blocks Ca2+ mobilization, abolished the QUIN responsiveness. Finally, the effect of D2S activation on K+ current was not modified by pretreatment of the cells with pertussis toxin. These results suggest that the D2s dopamine receptor expressed in NG108-15 cells inhibits the activity of native K+ current via a mechanism that is dependent upon the mobilization of intracellular Ca2+ and does not involve a pertussis toxin-sensitive G protein.
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PMID:Transfected D2 short dopamine receptors inhibit voltage-dependent potassium current in neuroblastoma x glioma hybrid (NG108-15) cells. 837 17

To study the mechanism underlying the effect of dopamine withdrawal on prolactin release, continuous perfusion experiments were performed on rat lactotroph-enriched primary cultures. Removal of dopamine (10(-7) M) after a short-term application (15 min) produced a rebound of prolactin secretion, which was enhanced by pretreatment of the cell culture with 17 beta-estradiol (10(-8) M for 48 h). Ca2+ channel blockade by Co2+ (1 mM) abolished the rebound in prolactin release. An increase in intracellular adenosine 3',5'-cyclic monophosphate by either forskolin (5 microM) or 3-isobutyl-1-methylxanthine (100 microM) enhanced the prolactin rebound after dopamine withdrawal. Application of thyrotropin-releasing hormone (10(-7) M) increased the prolactin rebound after dopamine withdrawal with a maximum effect obtained by commencing treatment immediately after removal of dopamine. Pretreatment of cell cultures with pertussis toxin (100 ng/ml, for 10 h) totally abolished the effects of dopamine on prolactin secretion. The dopamine agonist bromocriptine (10(-9) M) significantly decreased prolactin secretion, but no rebound effect was observed after its removal. We conclude that the rebound of prolactin release after dopamine treatment involves the influx of Ca2+.
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PMID:Mechanism of the prolactin rebound after dopamine withdrawal in rat pituitary cells. 839 90

Mystixin-7 and mystixin-11, small peptides structurally related to corticotropin-releasing factor (CRF), have been shown to attenuate vascular leakage in injured skin. The goal of this study was to characterize changes in cytosolic Ca2+ concentration ([Ca2+]i) in human epidermoid A-431 cells treated with these two peptides and to investigate the mechanisms by which these changes occurred. The resting [Ca2+]i in A-431 cells at 37 degrees C was 76 +/- 2 nM (n = 373). When cells were treated with either peptide, [Ca2+]i increased immediately. The increase depended on the peptide concentration, with a median effective concentration of 299 +/- 9 pM for mystixin-7 and 2.23 +/- 0.04 pM for mystixin-11. The increases also depended on extracellular Ca2+ and were blocked by Cd2+, Co2+, verapamil, and nifedipine. alpha-Helical CRF-(9-41), a synthetic CRF receptor antagonist, and pertussis toxin also blocked the increase in [Ca2+]i induced by the two peptides. Taken together, these results suggest that mystixin-7 and mystixin-11 interact with CRF receptors to activate pertussis-sensitive G proteins coupled to L-type Ca2+ channels that allow an uptake of extracellular Ca2+. Because U-73122, an inhibitor of 1,4,5-inositol trisphosphate production, partially inhibited the increase in [Ca2+]i, we measured inositol trisphosphates in cells stimulated by the two peptides. Both increased inositol trisphosphate levels within 1 min. The increase was inhibited by the removal of extracellular Ca2+ or treatment with U-73122. The results suggest that the Ca2+ influx stimulated by mystixin-7 and mystixin-11 induces an increase in inositol trisphosphates, resulting in a mobilization of Ca2+ from 1,4,5-inositol trisphosphate-sensitive Ca2+ pools.
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PMID:Mystixin-7 and mystixin-11 increase cytosolic free Ca2+ and inositol trisphosphates in human A-431 cells. 856 59

We report the identification and biochemical characterization of an endogenous m5 muscarinic acetylcholine receptor (mAChR) in the A2058 human melanoma cell line. This is the first demonstration of a m5AChR outside the central nervous system. The unusual effector coupling of this endogenous m5AChR is presented. The coding region amplified by polymerase chain reaction was identical to the known m5AChR sequence. Binding studies indicated a Kd of 99 +/- 6 pM and a Bmax of 45 +/- 4 fmol/mg membrane protein. This m5AChR coupled to stimulation of arachidonic acid release and to a 50% inhibition of forskolin-stimulated cAMP accumulation. The inhibition of cAMP production was insensitive to pertussis toxin treatment, but was dependent upon extracellular calcium. In contrast to the odd mAChR pattern, no cAMP was produced in response to carbachol (CC) stimulation. Moreover, no release of inositol phosphates could be measured after CC treatment despite the presence of at least 2 phospholipase C isoforms in A2058 cells. CC-stimulated arachidonic acid release (EC50 = 17.8 +/- 0.1 microM) was dependent upon external Ca2+, with marked reduction after coincubation with EGTA, Co2+, or high doses of verapamil (IC50 = 166 microM) or diltiazem (IC50 = 243 microM). Brief exposure to phorbol 12-myristate 13-acetate augmented CC-stimulated arachidonic acid release, whereas prolonged phorbol 12-myristate 13-acetate treatment resulted in down-regulation of release. Activation of the m5AChR resulted in Ca2+ influx that was attenuated by muscarinic antagonism and removal of extracellular Ca2+. A2058 cells exposed to CC had no alteration of cell shape or growth potential in monolayer culture, however, a statistically significant reduction in density-independent growth was observed over the range of CC concentrations from 0.1 to 100 microM. This endogenous m5AChR has a novel signal transduction coupling profile and receptor activation reduces clonogenic potential.
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PMID:Identification and molecular characterization of a m5 muscarinic receptor in A2058 human melanoma cells. Coupling to inhibition of adenylyl cyclase and stimulation of phospholipase A2. 866 91

GTP and AIF4- significantly stimulated the late phosphatidic acid (PA) formation induced by Clostridium perfringens alpha-toxin in rabbit erythrocyte lysates. Pertussis toxin blocked the PA production. AIF4- markedly enhanced phosphatidylethanol production induced by alpha-toxin in the presence of ethanol. GTP[gamma S] stimulated the PA formation and hemolysis induced by alpha-toxin, and GDP[beta S] inhibited them. An H-to-G mutation at position 126 (H126G) induced the PA formation and hemolysis in a Co2+ concentration-dependent manner. H148G induced neither the PA formation nor hemolysis. These results suggest that the toxin-induced hemolysis is due to activation of phospholipid metabolism systems through GTP-binding protein.
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PMID:Phospholipid metabolism induced by Clostridium perfringens alpha-toxin elicits a hot-cold type of hemolysis in rabbit erythrocytes. 875 53

The isolated perfused kidney of the rat was used to examine the contribution by guanosine triphosphate (GTP)-binding (G-) proteins, K+ and Ca2+ channels to the vasodilator actions of cryptolepine (5-methylquindoline). In normal Krebs-Henseleit buffer (4.7 mM KCl), cryptolepine elicited dose-dependent reductions in perfusion pressure of phenylephrine-preconstricted kidneys. The reductions in perfusion pressure by cryptolepine at bolus doses of 2.5, 5, and 10 micrograms were -18.0 +/- 3.4, -30.6 +/- 5.3, and -38.3 +/- 6.8 mm Hg, respectively (n = 19). In K(+)-free (0 mM KCl) Krebs-Henseleit solution, the vasodilator response to cryptolepine was reduced by 44.7 +/- 5.7% (n = 5; P < 0.01). The addition of ouabain (10(-4) M) further reduced cryptolepine-induced vasodilation to 63.0 +/- 7.2% (n = 11: P < 0.01) of the control. A combination of both conditions did not abolish the vasodilator responses to cryptolepine, suggesting the involvement of additional mechanisms. In 80, as opposed to 20 mM KCl, the reductions in perfusion pressure by cryptolepine, 2.5, 5, and 10 micrograms were markedly reduced to -0.8 +/- 0.8, -2.3 +/- 1.4, and -4.0 +/- 2.1 mm Hg, respectively (P < 0.01; n = 6). Responses to acetylcholine and diazoxide, an adenosine triphosphate (ATP)-dependent K+ channel activator, were also markedly reduced, suggesting the involvement of K+ channels for these agents. Furthermore, tetraethylammonium (5 and 10 mM), a non-specific K+ channel blocker, inhibited the vasodilator responses to cryptolepine (n = 5; P < 0.01) and to diazoxide and acetylcholine in a dose-related manner. However, glibenclamide (5 and 10 microM), an ATP-sensitive K+ channel blocker, inhibited the vasodilator responses to diazoxide and acetylcholine but was without effect on cryptolepine-induced vasodilation. This suggests that cryptolepine activates K+ channels which are tetraethyl ammonium- but not glibenclamide-sensitive. In pertussis toxin-treated rats, the vasodilator response to cryptolepine was not affected while that to acetylcholine and especially diazoxide was markedly inhibited. This suggests that, unlike diazoxide and acetylcholine, the K+ channels activated by cryptolepine are not coupled to pertussis toxin-sensitive G-proteins. In the presence of verapamil (5 microM) and cobalt chloride (1 mM), Ca2+ channel blockers, the vasodilator response to cryptolepine was inhibited (n = 5; P < 0.01), suggesting that Ca2+ flux across membranes is also involved in cryptolepine-induced vasodilation in the rat kidney.
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PMID:Cryptolepine-induced vasodilation in the isolated perfused kidney of the rat: role of G-proteins, K+ and Ca2+ channels. 884 4

1. Transient outward current was recorded in cultured frog melanotrophs with the whole-cell configuration of the patch-clamp technique. The ionic dependence, kinetics and pharmacological properties of the current were studied. The effects of the A1 adenosine receptor agonist R-N6-phenylisopropyl-adenosine (R-PIA) on this current were also investigated. 2. In tetrodotoxin- and cobalt-containing solution, depolarization from -120 mV elicited both transient and delayed outward currents. Pulses from -60 mV activated only a sustained late current. 3. 4-Aminopyridine (4 mM) reduced the transient outward current much more than the delayed outward current. In contrast, tetraethylammonium (10-20 mM) selectively reduced the delayed current. 4. Tail current measurements showed a positive shift in the reversal potential when external K+ concentration was increased, indicating that K+ was the predominant charge carrier. 5. Steady-state inactivation was complete at potentials positive to -10 mV and removed by hyperpolarization. 6. Inactivation of the transient current was slowed and accelerated in oxidizing and reducing conditions, respectively, confirming the involvement of an inactivating 'ball and chain' peptide. 7. R-PIA increased the transient current. The steady-state inactivation curve was shifted towards more positive potentials without changing the activation kinetics. Pretreatment with pertussis toxin (1 microgram ml-1) blocked the response to R-PIA. 8. It is concluded that frog melanotrophs possess an A-type current that is likely to play an important role in excitability. This current, which is directly modulated by A1 adenosine receptors through a Gi/G(o) protein, appears to be responsible for the inhibitory effects of adenosine on electrical activity.
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PMID:A-type potassium current modulated by A1 adenosine receptor in frog melanotrophs. 884 38


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