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)

Second messenger signaling has been shown to regulate a variety of cellular functions in response to external stimuli. The following study was performed to determine the potential role of second messengers on influencing lipoprotein uptake by the arterial wall. An aortic endothelial cell (EC)-smooth muscle cell (SMC) bilayer was preexposed to various mediators of the cyclic AMP and inositol phosphate pathways for 30 min. The permeability, binding, and cellular uptake of 125I-labeled low-density lipoprotein (LDL) (10 micrograms/ml) added to the upper well media of the bilayer were then measured for each cell type after a 3-h incubation period. Forskolin (100 microM), an activator of adenylate cyclase, resulted in an increase in all measured parameters. 8-Br-cAMP (30 microM), a cAMP analogue, showed a similar effect on EC permeability (P < 0.00005) while galanin (0.1 mg/ml), an adenylate cyclase inhibitor, had no effect. GTP-binding protein inhibition with pertussis toxin (10 mg/ml) led to a marked reduction in SMC uptake (P < 10(-7)) without affecting membrane binding. Protein kinase C activation with phorbol myristate acetate (0.1 mg/ml) also increased EC permeability to LDL but, unlike forskolin, had no effect on LDL binding. This effect was further potentiated by calcium ionophore A23187 (5 x 10(-6) M), indicating a contributing role of intracellular calcium. These results would suggest that LDL uptake can be influenced by several second messenger systems, and that EC and SMC may respond differently to these intracellular signals. Second messenger regulation may allow changes in lipoprotein uptake by the arterial wall in response to external stimuli.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Second messenger regulation of lipoprotein uptake by an arterial wall model. 769 36

The adenosine A2a receptor inhibition of potassium (15 mM)-evoked GABA release from striatal nerve terminals has been examined. High extracellular calcium concentrations (4 mM) reduced the effect of the A2a receptor agonist CGS-21680 (1 nM). CGS-21680 inhibited GABA release in the presence of the L-type calcium channel blocker nifedipine, which itself inhibited evoked GABA release (by 16 +/- 4%). omega-Conotoxin inhibited the evoked release by 45 +/- 4% and prevented the action of CGS-21680. Forskolin and 8-bromo cyclic AMP both stimulated evoked GABA release at low concentrations, but at higher concentrations they abolished the inhibition by CGS-21680 without affecting the evoked release. The nonselective protein kinase inhibitor H-7 inhibited both the evoked release and the inhibition by CGS-21680, whereas the selective protein kinase A and G inhibitor HA-1004 had no effect on either evoked release or the action of CGS-21680. Pretreatment with pertussis toxin did not affect the A2a receptor-mediated inhibition. Therefore, the effect of A2a receptor stimulation was not mediated by protein kinases A or G but was inhibited by elevated cyclic AMP levels and mimicked by inhibitors of the N-type calcium channel and protein kinase C.
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PMID:Inhibition of striatal GABA release by the adenosine A2a receptor is not mediated by increases in cyclic AMP. 776 61

We investigated the mechanism of Cl- secretion by fluoroaluminate(AlF4-) and sodium orthovanadate(vanadate) using the human colonic T84 cell line. T84 cell monolayers grown on collagen-coated filters were mounted in Ussing chambers to measure short circuit current(ISC). Serosal addition of AlF4- or vanadate to T84 monolayers produced a sustained increase in ISC. Removal of Ca2+ from the serosal bathing solution partially inhibited AlF4-(-)and vanadate-induced ISC, and readministration of Ca2+ restored AlF4-(-)and vanadate-induced ISC. Carbachol application in the presence of forskolin, AlF4- or vanadate induced a synergistic increase of ISC. Forskolin and vanadate significantly increased cellular cAMP level, while carbachol and AlF4- did not. Carbachol, AlF4- and vanadate significantly increased [Ca2+]i. After Na+ in mucosal bathing solution was replaced with K+, and the mucosal membrane of T84 cell was permeabilized with amphotericin B, AlF4-, vanadate, and carbachol increased K+ conductance, but forskolin did not. After sodium chloride in serosal bathing solution was replaced with sodium gluconate and the serosal membrane was permeabilized with nystatin, forskolin, AlF4-, and vanadate increased Cl- conductance, but carbachol did not. AlF4-(-)induced ISC was remarkably inhibited by the pretreatment of pertussis toxin(2 micrograms/ml) for 2 hours. These results indicate that AlF4- and vanadate can increase Cl- secretion via simultaneous stimulation of Cl- channel and K+ channel in T84 cells. However, the AlF4- action is mostly attributed to stimulation of pertussis toxin-sensitive G-proteins, whereas the vanadate action mostly results from G protein-independent mechanisms.
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PMID:Stimulation of Cl- secretion by AlF4- and vanadate in T84 cells. 778 47

Activation of muscarinic receptors has been shown to inhibit L-type calcium conductances by mechanisms sensitive to pertussis toxin (PTX). In this study we show that agonist stimulation of the m4 muscarinic receptor leads to an increase in an L-type calcium conductance in the AtT-20 pituitary cell line, by a PTX-sensitive mechanism. The amplitude of the dihydropyridine (DHP)-sensitive or L-type calcium current was increased by acetylcholine (ACh), with no shift in the voltage dependence. This action of ACh was completely inhibited by PTX pre-treatment. Forskolin, cAMP and phorbol 12,13-dibutyrate reduced, while RpcAMPs, an inhibitor of cAMP-dependent protein kinase (PKA), increased the L-type calcium conductance. We propose that the m4 muscarinic receptor activates the L-type calcium channel by inhibition of adenylyl cyclase resulting in reduced cAMP levels and, hence, reduced PKA activity. This novel increase in calcium current via the m4 muscarinic receptor appears to reflect the coupling with an L-type channel of the D class, due to the sensitivity of the L-type calcium conductance to both DHPs and omega-conotoxin, and, thus, is distinct from the skeletal muscle and cardiac L-type channels of the C class previously studied.
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PMID:Enhancement of an L-type calcium current in AtT-20 cells; a novel effect of the m4 muscarinic receptor. 779 45

Cholinergic inhibition of atrial contraction is typically followed by a rebound positive inotropic response. In the present study, we used a nystatin-perforated patch whole-cell recording method to determine whether acetylcholine (ACh) elicits a rebound stimulation of L-type Ca2+ current (ICa,L) in cat atrial myocytes. ACh (1 mumol/L) decreased basal ICa,L (-19 +/- 2%). Within approximately 30 s of returning to ACh-free solution, basal ICa,L exhibited a rebound increase above the control level (+61 +/- 7%) that returned to the control level within 4 to 5 minutes. ACh elicited concomitant changes in cell shortening, ie, a decrease followed by a rebound increase. The EC50 and maximal response of ACh-induced inhibition and rebound stimulation of ICa,L were 1.9 x 10(-9) mol/L and -30%, respectively, and 2.9 x 10(-8) mol/L and +64%, respectively. All effects of ACh on ICa,L were blocked by prior exposure to 1 mumol/L atropine or 100 mumol/L AFDX116 and unaffected by 0.2 mumol/L pirenzepine or 1 mumol/L propranolol. In the presence of ACh, exposure to atropine elicited stimulation of ICa,L.ACh-induced inhibition and rebound stimulation of current were independent of external Ca2+. Rebound stimulation of ICa,L was associated with a negative shift in the voltage dependence of ICa,L activation. Inhibition of protein kinase A by 50 mumol/L Rp-cAMPs decreased basal ICa,L by 36 +/- 1% and abolished the rebound stimulation of ICa,L. Forskolin (0.01 mumol/L) or isoproterenol (0.01 mumol/L) had no effect on basal ICa,L, but each accentuated the rebound increase in ICa,L. When adenylate cyclase was maximally stimulated with 1 mumol/L isoproterenol plus 2 mumol/L forskolin, ACh decreased ICa,L but failed to elicit rebound stimulation of ICa,L. Milrinone (10 mumol/L) increased basal ICa,L by 70 +/- 7% and significantly attenuated the rebound stimulation of ICa,L. Exposure to 1 mmol/L 8-bromo-cGMP elicited a small decrease in basal ICa,L, attenuated ACh-induced inhibition, and enhanced the rebound stimulation of ICa,L. Incubation in pertussis toxin prevented all ACh-induced changes in ICa,L. Inhibition of nitric oxide synthase by 100 mumol/L NG-monomethyl-L-arginine (L-NMMA) decreased basal ICa,L by -20 +/- 5%, prevented ACh-induced inhibition, and markedly attenuated the rebound stimulation of ICa,L. We conclude that in cat atrial myocytes ACh acts via M2 muscarinic receptors and pertussis toxin-sensitive G protein to inhibit basal ICa,L and that on withdrawal ACh elicits a rebound stimulation of ICa,L. Rebound stimulation of ICa,L is mediated via cAMP-dependent protein kinase A enhanced by ACh-induced inhibition of phosphodiesterase.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Acetylcholine elicits a rebound stimulation of Ca2+ current mediated by pertussis toxin-sensitive G protein and cAMP-dependent protein kinase A in atrial myocytes. 789 37

In the present study we investigated the effects of the somatostatin (SS) analogs octreotide, RC-160, and BIM-23014 on GH release by cultured cells of human GH-secreting pituitary tumors, in normal rat anterior pituitary cells, and on gastrin release by cultured cells from a human gastrinoma. In all GH-secreting adenomas and in rat anterior pituitary cells, RC-160 was the most potent compound. RC-160 significantly inhibited GH-, PRL, and/or alpha-subunit release by human GH-secreting pituitary adenoma cells in concentrations as low as 10(-12)-10(-14) M, whereas at the same concentrations, octreotide and BIM-23014 did not inhibit or were significantly less effective in inhibiting GH release (P < 0.01, RC-160 vs. octreotide and BIM-23014). In rat anterior pituitary cell cultures, the IC50 values for inhibition of GH release were, in rank order of potency, 0.1, 5.3, 47, 48, and 99 pM for RC-160, SS-14, BIM-23014, octreotide, and SS-28, respectively. Maximal inhibitory effects by the three analogs were the same in the human GH adenoma cell cultures and the rat anterior pituitary cell cultures (-60%). On the basis of these data, RC-160 appears to be about 500 times more potent than octreotide and BIM-23014 in inhibiting GH release by rat anterior pituitary cells in vitro. Forskolin (100 microM) as well as pretreatment of the cells with pertussis toxin significantly diminished the inhibitory effects of the three SS analogs and those of SS-14 and SS-28 to the same extent. The latter data suggest that octreotide, RC-160, and BIM-23014 act mainly via a pertussis toxin-sensitive G-protein and an adenylyl cyclase-dependent mechanism. In the human gastrinoma culture, RC-160 inhibited gastrin release significantly more than octreotide at 10(-12)- and 10(-14)-M concentrations (P < 0.01). In conclusion, the SS analogs octreotide, RC-160, and BIM-23014 may have significant different potencies of inhibition of hormone release in vitro, with RC-160 being the most potent SS analog and octreotide and BIM-23014 having similar potencies. Depending on the pharmacokinetic properties of these three octapeptide SS analogs, these observations may have consequences for the medical therapy of patients with SS receptor-positive endocrine tumors.
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PMID:Relative potencies of the somatostatin analogs octreotide, BIM-23014, and RC-160 on the inhibition of hormone release by cultured human endocrine tumor cells and normal rat anterior pituitary cells. 790 31

The effects of pertussis toxin, forskolin, and cAMP analogues on the antinociceptive action of nicotine were examined to investigate the possible involvement of adenylate cyclase and G-proteins in nicotine's antinociceptive effect. Intrathecal injection of pertussis toxin (0.25 and 0.50 micrograms) in mice inhibited nicotine-induced antinociception in the tail-flick test. The effect of the toxin was dose and time dependent. Forskolin, a potent adenylate cyclase activator, and 8-(-4-chlorophenylthio) adenosine-3':5' monophosphate, cyclic (8-CPT-cAMP), a cAMP analogue, inhibited the antinociceptive effects of nicotine in a dose-dependent manner. EGTA reversal of 8-CPT-cAMP's inhibitory effects suggests that calcium may to be involved. These data implicate the possible involvement of a G-protein and a second messenger system (activation of a cAMP-dependent protein kinase and increase in cyclic AMP levels) in nicotine-induced analgesia in mice.
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PMID:Nicotine-induced antinociception in mice: role of G-proteins and adenylate cyclase. 802 3

Incubation of dispersed adenohypophyseal cells from intact male rats with Neuropeptide Y (NPY) or Peptide YY (YY) at 21 degrees C increased maximal 125I LHRHa binding (Bmax) by about 50%. In presence of 10(-7) M NPY, Bmax calculated from saturation isotherm curves was 15.3 +/- 1.9 fmoles x mg-1 proteins, as compared to 10 +/- 1 fmoles x mg-1 in control incubates. The increase was dose dependent with an EC50 of 6.3 +/- 1.8 10(-10) M NPY. Preincubation of the cells with pertussis toxin (PT, 15 ng/ml) for 24 h abolished the effect, suggesting coupling of NPY receptors to G alpha o or G alpha i proteins. NPY 10(-7) M inhibited basal and Forskolin 10(-5) M stimulated intracellular cyclic AMP formation by 31.9 +/- 3.4% and 30.6 +/- 2.3% respectively. Desensitization of protein kinase C by overnight preincubation of the cells with 10(-6) M phorbol ester (PMA) did not interfere with the effect of NPY. In contrast, W7, a calmodulin inhibitor, as well as H7, a protein kinase C inhibitor with a relatively wide spectrum, suppressed the effect of NPY with IC50 of 1.4 +/- 0.6 10(-6) M and 2.2 +/- 0.5 10(-5) M, respectively. Taken together, these results suggest that NPY is able to control unmasking of a cryptic LHRH receptor pool in pituitary cells by a process dependent upon both GTP binding proteins and calmodulin dependent protein kinase.
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PMID:Neuropeptide Y enhances LHRH binding to rat gonadotrophs in primary culture. 817 May 23

PTH-related protein (PTHrP), the major mediator of hypercalcemia of malignancy, reduces tubular phosphate (Pi) reabsorption through its PTH-like renotropic actions. Another peptide detected in tumoral cells, transforming growth factor-beta (TGF beta), has been shown to considerably suppress the sodium-dependent Pi transport system present in the apical membrane of renal epithelial cells. The unexplored interactions between TGF beta and PTHrP were examined in opossum kidney (OK) cells. Using confluent OK cells, we showed that TGF beta attenuated the inhibition of Pi transport mediated by PTHrP. Similarly, 18 h TGF beta incubation resulted in a substantial reduction of the cAMP response elicited by PTHrP without apparent involvement of pertussis toxin-sensitive guanine nucleotide binding protein(s). The number of PTHrP(1-34) binding sites in TGF beta-treated cells was decreased with the affinity unchanged. Forskolin- and prostaglandin E2-stimulated cAMP productions were not significantly altered by TGF beta treatment. Therefore, TGF beta reduced Pi transport in OK cells, modulated the actions of PTHrP, and decreased its receptor number. Whether this happens in vivo is as yet unknown.
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PMID:Transforming growth factor-beta modulates the parathyroid hormone-related protein-induced responses in renal epithelial cells. 839 20

Neuropeptide Y (NPY) and its encoding mRNA were measured in neurons co-cultured from rat basal forebrain and cerebral cortex. NPY was synthesized and released in a manner consistent with secretion-synthesis coupling; depolarization increased each in a calcium-dependent manner. The accumulation of NPY encoding mRNA was elevated by a muscarinic receptor blocker, without changes in transmitter release or peptide synthesis, thereby consistent with a membrane potential-independent mechanism. Changes in intrinsic muscarinic transmission could nonetheless be expressed rapidly as an elevation in NPY levels by depolarizing the neurons subsequent to muscarinic receptor blockade. This depolarization-induced elevation of NPY subsequent to muscarinic receptor blockade was dependent on the presence of extracellular calcium ions. Forskolin and pertussis toxin also increased NPY encoding mRNA levels in a manner that was not additive with muscarinic receptor blockade. These results suggest that one or more muscarinic receptors may tonically modulate NPY synthesis via changes in adenylate cyclase activity, providing a model for the non-homeostatic modulation of neuropeptide turnover.
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PMID:Modulation of neuropeptide Y expression in rat brain neuronal cultures. 840 72


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