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)

The production of inositol phosphates in response to carbachol was studied in rat anterior pituitary tissue prelabelled with [3H]inositol. Carbachol (10 microM) stimulated inositol mono-, bis- and trisphosphate production (IP1, IP2 and IP3) by 360 +/- 49, 338 +/- 49 and 503 +/- 49 (mean +/- SEM, P less than 0.001) percent respectively during a 30 min incubation. Mean basal production was 5.4 +/- 0.3, 4.1 +/- 0.5 and 0.9 +/- 0.3 expressed as a percent of total [3H]inositol lipid for IP, IP2 and IP3 respectively. Stimulated inositol phosphate production was dose dependent and detectable after 5 min. Atropine prevented this stimulation indicating mediation via muscarinic receptors. Removal of extracellular Ca2+ reduced both basal and stimulated total inositol phosphate production by 60% and 56% respectively but did not impair carbachol-induced phosphoinositide hydrolysis per se. Pretreatment of pituitary tissue with either somatostatin (5 micrograms/ml) or pertussis toxin (1 microgram/ml) had no effect on either basal or stimulated inositol phosphate production. These results demonstrate a cholinergic stimulation of phosphatidylinositol bisphosphate (PIP2) hydrolysis in the anterior pituitary which may be important in the action of cholinergic agonists on pituitary hormone secretion.
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PMID:Cholinergic stimulation of phosphoinositide hydrolysis in rat anterior pituitary. 289 24

Development of an enriched cultured cell system allowed us to investigate the mechanism of cholinergic inhibition of somatostatin release stimulated by adenosine 3',5'-cyclic monophosphate (cAMP) and Ca2+-protein kinase C-dependent pathways of cell activation. After a 24-h culture on rat tail collagen, D-cells, quantified by immunohistochemistry, were 18-fold enriched compared with unelutriated dispersed cells. Somatostatin release from cultured cells was expressed as a percent of the somatostatin released by a specific stimulus in control cells. Under basal conditions release of somatostatin was 2.3 +/- 0.6% of the total cell content. Epinephrine (1 microM) and cholecystokinin octapeptide (10 nM) increased somatostatin release to 6.98 +/- 1.25 and 10.72 +/- 1.64%, respectively. Carbachol (1 microM) completely inhibited somatostatin release stimulated by epinephrine and reduced cholecystokinin octapeptide-stimulated release to 75% of control levels. Carbachol inhibition of the response to both epinephrine and cholecystokinin octapeptide was totally prevented by 5 h of treatment of the cells with pertussis toxin (300 ng/ml). Somatostatin release in response to the diterpene forskolin (10 microM), dibutyryl cAMP (300 microM), the phorbol ester beta-phorbol 12-myristate 13-acetate (0.1 microM), and the calcium ionophore A23187 (1 microM) was also inhibited by carbachol and prevented by pertussis toxin pretreatment. The ADP-ribosylase inhibitor isonicotinamide (1 mM) selectively blocked the effect of pertussis toxin without altering other stimulatory or inhibitory responses. These data are consistent with the view that carbachol inhibits somatostatin release at guanyl nucleotide-binding protein and/or another pertussis toxin-sensitive site.
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PMID:Pertussis toxin-sensitive cholinergic inhibition of somatostatin release from canine D-cells. 290 2

Dopamine inhibits and serotonin stimulates adenylate cyclase activity in a neuroblastoma X Chinese hamster brain explant cell line (NCB-20). The inhibition of cyclic AMP accumulation by dopamine was blocked by pretreatment of the cells with pertussis toxin. Carbachol and bradykinin stimulated the accumulation of water-soluble inositol phosphates whereas thyrotropin-releasing hormone, vasopressin, neurotensin, and phenylephrine were without effect. Dopamine and serotonin had no significant effect on carbachol-induced phosphoinositide hydrolysis or the levels of the parent lipids within the membrane. Forskolin induced a much larger stimulation of cyclic AMP than did serotonin, and caused an increase in the levels of phosphatidylinositol-4-phosphate and phosphatidyl inositol-4,5-bisphosphate in the cell membrane.
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PMID:Activation of dopamine receptors does not affect phosphoinositide turnover in NCB-20 cells. 303 93

The GTP binding regulatory protein (Ni involved in adenylate cyclase inhibition was purified from rat brain and reconstituted, together with muscarinic cholinergic receptors purified from porcine brain, into phospholipid vesicles. Guanosine 5'-O-(3-[35S]thio)-triphosphate ([35S]GTP gamma S) binding and GTP hydrolyzing activities of reconstituted Ni were stimulated by the addition of a muscarinic agonist, carbachol. The effect of carbachol was to increase the Vmax values of these activities, but the Km values were also increased slightly in most cases. Carbachol bound to vesicles with the same order of magnitude of Km as that for stimulation of GTPase. The affinity of this binding was reduced by GTP gamma S, indicating that the high-affinity receptor-Ni complex was formed in a GTP-dependent manner in reconstituted vesicles. Incubation of Ni with NAD and islet-activating protein (IAP), pertussis toxin, caused ADP-ribosylation of the alpha-subunit of Ni. The criteria for the receptor-Ni interaction, i.e. carbachol stimulation of the activities of Ni and the GTP gamma S effect on carbachol binding, were no longer observed, when this IAP-treated Ni, instead of the nontreated Ni, was reconstituted into vesicles, though there was no difference between IAP-treated and nontreated Ni in their basal activities observable without carbachol. No, the protein with a character very similar to Ni in rat brain, was also coupled to muscarinic receptors when they were reconstituted into vesicles under the same conditions. Thus, GTP-binding proteins serving as the substrate of IAP-catalyzed ADP-ribosylation are capable of interaction functionally with muscarinic receptors in phospholipid vesicles.
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PMID:Functional interaction of purified muscarinic receptors with purified inhibitory guanine nucleotide regulatory proteins reconstituted in phospholipid vesicles. 308 83

Purified porcine atrial muscarinic receptor (mAcChR) was reconstituted with purified porcine atrial inhibitory guanine nucleotide binding protein (Gi) in a lipid mixture consisting of phosphatidylcholine, phosphatidylserine, and cholesterol (1:1:0.1 w/w). 5'-Guanylyl imidodiphosphate (0.1 mM) had no effect on the binding of the muscarinic antagonist L-quinuclidinyl benzilate but converted high-affinity carbachol binding sites (Kd equal to 1 microM) in the reconstituted preparation to the low-affinity state (Kd equal to about 100 microM). Steady-state kinetic measurements of GTPase activity showed that the turnover number was increased from 0.19 min-1 in the presence of the muscarinic antagonist L-hyoscyamine to 2.11 min-1 for the agonist carbachol. The affinity of Gi for GDP was reduced by about 50-fold upon interaction with the carbachol-mAcChR complex, and the observed rate constant for GDP dissociation was increased by 38-fold from 0.12 to 4.5 min-1. Thus, the increase in steady-state GTPase activity observed for muscarinic agonists is largely, if not exclusively, due to the increase in GDP dissociation from Gi--probably the rate-limiting step in the steady-state mechanism. Carbachol-stimulated GTPase was sensitive to ADP-ribosylation of the reconstituted Gi by pertussis toxin, but the high-affinity agonist binding was uncoupled only when the reconstituted preparation was treated with pertussis toxin in the presence of GTP and the agonist acetylcholine. These results suggest that association with the mAcChR protects Gi from ADP-ribosylation by pertussis toxin.
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PMID:Reconstitution of the purified porcine atrial muscarinic acetylcholine receptor with purified porcine atrial inhibitory guanine nucleotide binding protein. 312 98

Direct effects of islet-activating protein (IAP), pertussis toxin, on membrane preparations from rat heart tissues were studied. The native IAP was without effect, but its A-protomer, an active subunit, was effective after reduction of disulfide bonds in the peptide chain; it catalyzed ADP-ribosylation of the membrane Mr = 41,000 protein. Simultaneously, muscarinic receptor-mediated inhibition of adenylate cyclase was abolished. Carbachol, an agonist of muscarinic receptors, bound to membranes with the Hill coefficient smaller than unity. The affinity for the carbachol binding was lowered and the Hill coefficient was increased by guanylylimidodiphosphate (Gpp(NH)p), reflecting the muscarinic receptor coupling to the guanine nucleotide regulatory protein (N). Carbachol bound to the A-promoter-treated membranes with a lower affinity and a higher Hill coefficient, and these kinetic values were not altered by Gpp(NH)p, indicating that treatment of membranes with the A-protomer of IAP uncoupled muscarinic receptors from N. This IAP-sensitive N is Ni involved in the cyclase inhibition. Neither beta-adrenergic activation of adenylate cyclase nor beta-agonist binding to membranes was affected by the A-protomer of IAP. Thus, N (Ns) coupled to beta-receptors is not the site of its action. Although the affinity and the Hill coefficient for beta-agonist binding was not affected by preactivated cholera toxin either, the effect of Gpp(NH)p to alter these kinetic parameters was much smaller in the cholera toxin-treated membranes than in non-treated membranes. Thus, cholera toxin modified beta-receptor coupling to Ns in a manner quite different from IAP-induced modification of muscarinic receptor coupling to Ni.
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PMID:Functional uncoupling of muscarinic receptors from adenylate cyclase in rat cardiac membranes by the active component of islet-activating protein, pertussis toxin. 668 24

We investigated the effects of added beta gamma subunits of G proteins (G beta gamma) on beta-adrenergic responsiveness of transmembrane Ca2+ currents (ICa) in ventricular myocytes from neonatal rabbits. G beta 1 gamma 1 purified from retinal rods was dialyzed into cells via the voltage clamp micro-electrode. Stimulation of ICa by isoproterenol was not affected by added intracellular G beta 1 gamma 1 or by carbachol alone but was completely blocked by combined G beta 1 gamma 1 and carbachol. Pretreatment of cells with pertussis toxin or temporal separation of carbachol and isoproterenol allowed stimulation of ICa by isoproterenol in cells dialyzed with G beta 1 gamma 1. Carbachol and G beta 1 gamma 1 together also did not prevent stimulation of ICa by dibutyryl-cyclic AMP. Thus, rather than simply inactivating Gs alpha by mass action, G beta 1 gamma 1 acts in concert with carbachol to inhibit isoproterenol stimulation of ICa.
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PMID:Adenylyl cyclase integrates multiple G protein signals to modulate calcium currents in neonatal rabbit heart. 748 87

Carbachol (10(-6)-3X10(-4)M) induces a positive inotropic response in paced, pertussis toxin-treated fibers which is atropine-sensitive and independent of endogenous catecholamines. At the same concentrations in atria from saline-treated chicks, carbachol's negative inotropic effect on the steady state contractions (SSC) is attenuated and the rested state contraction (RSC) is increased. The RSC and SSC in pertussis toxin-treated fibers are increased by carbachol (EC50 = 30 microM) indicating that repetitive electrical depolarization is not essential for the inotropic response. The inotropic response of the SSC is frequency-independent from 0.10-1.0 Hz; however it is decreased (approximately 50%) at a high frequency (3.0 Hz). In control untreated atrial muscle, carbachol (10(-4)M) selectively increases the early component of the RSC. The late component of the RSC, representing activation of transmembrane Ca2+ inward current, is not changed. Carbachol's positive inotropic effect is perhaps exerted by enhancing Ca2+ release and/or Ca2+ content of the sarcoplasmic reticulum. The ability of various muscarinic agonists to induce a positive inotropic response was: carbachol > acetylcholine > oxotremorine. This order correlates with the ability of these agents to induce a tetrodotoxin-resistant Na+ inward current that increases intracellular Na+ and to promote phosphatidylinositol hydrolysis. These data are consistent with the hypothesis that the carbachol-induced positive inotropic response may result from greater intracellular Ca2+ availability secondary to enhanced Na-Ca exchange. The greater Ca2+ availability, together with increased production of the Ca-mobilizing messenger, inositol 1,4,5-trisphosphate (InsP3), can exert a synergistic effect to regulate force generation.
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PMID:Muscarinic agonist-induced positive inotropic response in chick atria. 749 Oct 95

1. Smooth muscle fragments from the longitudinal layer of the small intestine of the guinea-pig were permeabilized with Staphylococcus aureus alpha toxin (alpha-toxin) and used to investigate the role of G-protein activation in the regulation of muscarinic acetylcholine receptor (AChR)-stimulated inositol phospholipid hydrolysis. 2. The efficiency of alpha-toxin permeabilization was estimated by the release of [3H]-2-deoxyglucose ([3H]-2DG) after prior loading or lactate dehydrogenase (LDH) enzyme release from the smooth muscle fragments. 3. In alpha-toxin-permeabilized smooth muscle, but not in non-permeabilized muscle, GTP gamma S induced time- and concentration-dependent increases in labelled inositol phosphates. Carbachol (CCh) increased labelled inositol phosphates in both permeabilized and non-permeabilized muscle, although the increases were greater in non-permeabilized smooth muscle. The response to 100 microM CCh was severely reduced by 0.5 microM atropine. 4. In permeabilized muscle the effects of GTP gamma S or CCh on inositol phosphate levels were reduced by treatment with pertussis toxin (PTX) and completely inhibited by GDP beta S. 5. GTP gamma S caused a concentration-dependent inhibition of the CCh-induced increases in the levels of labelled inositol phosphates. Dibutyryl cyclic AMP or Sp-cAMPs (adenosine-3',5'-cyclic phosphorothiolate-Sp) reduced the effects of CCh on inositol phosphate levels. 6. The results suggest that muscarinic AChR activation induces inositol phospholipid hydrolysis via more than one G-protein in this smooth muscle and that several mechanisms may contribute to the modulation of both stimulatory and inhibitory responses observed.
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PMID:Effects of GTP gamma S on muscarinic receptor-stimulated inositol phospholipid hydrolysis in permeabilized smooth muscle from the small intestine. 764 69

We investigated the effects of the M-cholinoceptor agonist carbachol on cyclic GMP (cGMP) content and contractile response in the absence and presence of the nitric oxide synthase inhibitor NG-nitro-L-arginine in guinea-pig isolated ventricular cardiomyocytes. Carbachol (10 mumol/l, 10 min) increased basal cGMP content to approximately 200% and contractile response to 118%. Preincubation of the cardiomyocytes with NG-nitro-L-arginine (0.1 mumol/l, 60 min) did not alter the effects of carbachol on neither cGMP content or contractile response. Moreover, nitric oxide synthase activity was undetectable in crude or ADP-agarose purified cytosolic and particulate fractions of homogenized isolated ventricular cardiomyocytes. Pretreatment with pertussis toxin did not affect the carbachol-mediated increase in cGMP content or contractile response. However, methylene blue abolished the elevation in cGMP content by carbachol, without changing contractile response. It is concluded that the carbachol-mediated increase in cGMP content and contractile response in ventricular cardiomyocytes is neither mediated via a nitric oxidebiosynthesis pathway nor via a pertussis toxin-sensitive GTP-binding protein. Furthermore, the cGMP increase by carbachol is due to an activation of soluble guanylyl cyclase and is dissociated from the contractile response. We therefore assume that carbachol activates two independent effector cascades, one leading to an elevation in cGMP content and the other to an increase in contractile response and that none of the effects are mediated via endogenous nitric oxide formation.
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PMID:Ca(++)-dependent constitutive nitric oxide synthase is not involved in the cyclic GMP-increasing effects of carbachol in ventricular cardiomyocytes. 768 6


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