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 mechanisms by which neuropeptide Y (NPY) mediates its postsynaptic actions on the guinea-pig uterine artery, were investigated by incubating arterial segments in culture medium containing pertussis toxin (PTX). Arteries were incubated with 0, 0.25 or 1 microgram.ml-1 PTX for 24 or 48 h. Arterial segments incubated in culture medium without PTX showed the three postsynaptic responses to NPY which were reported previously in uncultured arteries: NPY further contracted segments which were precontracted with prostaglandin F2 alpha; NPY reduced the maximum relaxations produced by vasoactive intestinal peptide (VIP); and NPY produced a rightward shift in the VIP concentration-response curves. PTX attenuated the three actions of NPY on the uterine artery to different degrees. PTX also reduced the magnitude of contractions produced by prostaglandin F2 alpha, but did not affect contractions produced by 0.126 M KCl, or relaxations produced by VIP in the absence of NPY. These data indicate that all postsynaptic actions of NPY on the uterine artery, and contractions produced by prostaglandin F2 alpha, are at least partly mediated by pertussis toxin-sensitive GTP-binding proteins. It is not clear whether these multiple actions of NPY are mediated by one, or more than one, GTP-binding protein.
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PMID:Pertussis toxin attenuates postsynaptic actions of neuropeptide Y on the guinea-pig uterine artery. 180 Jan 21

Calcium (Ca2+) ion concentrations that are achieved intracellularly upon membrane depolarization or activation of phospholipase C stimulate adenylate cyclase via calmodulin (CaM) in brain tissue. In the present study, this range of Ca2+ concentrations produced unanticipated inhibitory effects on the plasma membrane adenylate cyclase activity of GH3 cells. Ca2+ concentrations ranging from 0.1 to 0.8 microM exerted an increasing inhibition on enzyme activity, which reached a plateau (35-45% inhibition) at around 1 microM. This inhibitory effect was highly cooperative for Ca2+ ions, but was neither enhanced nor dependent upon the addition of CaM (1 microM) to EGTA-washed membranes. The inhibition was greatly enhanced upon stimulation of the enzyme by vasoactive intestinal peptide (VIP) and/or GTP. Prior exposure of cultured cells to pertussis toxin did not affect the inhibition of plasma membrane adenylate cyclase activity by Ca2+, although in these membranes, hormonal (somatostatin) inhibition was significantly attenuated. Maximally effective concentrations of Ca2+ and somatostatin produced additive inhibitory effects on adenylate cyclase. The addition of phosphodiesterase inhibitors demonstrated that inhibitory effects of Ca2+ were not mediated by Ca2(+)-dependent stimulation of a phosphodiesterase activity. These observations provide a mechanism for the feedback inhibition by elevated intracellular Ca2+ levels on cAMP-facilitated Ca2+ entry into GH3 cells, as well as inhibitory crosstalk between Ca2(+)-mobilizing signals and adenylate cyclase activity.
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PMID:Potent and cooperative feedback inhibition of adenylate cyclase activity by calcium in pituitary-derived GH3 cells. 197 2

This study tests the hypothesis that atrial natriuretic factor (ANF) and C-ANF(4-23)-NH2 (C-ANF) augment cGMP generation and inhibit both cAMP generation and depolarization-induced catecholamine release in nerve growth factor treated pheochromocytoma cells by a pertussis toxin (PTX)-sensitive mechanism. Synthetic rat ANF(99-126) and the clearance receptor antagonist C-ANF (10(-12)-10(-9) M) inhibited basal and 5 microM vasoactive intestinal peptide (VIP)-induced cAMP generation in a concentration-dependent manner. These actions of ANF and C-ANF were blocked by 12-18 h pretreatment with PTX (100 ng/ml), suggesting ANF receptor coupling to adenylate cyclase via an inhibitory guanine nucleotide-binding protein. Both ANF (10(-11)-10(-9) M) and C-ANF (10(-11)-10(-8) M) also inhibited K(+)-induced catecholamine release in a concentration-dependent manner. ANF (10(-11)-10(-8) M) increased cGMP generation in a concentration-dependent manner but C-ANF did not. The accumulation of cGMP in response to ANF was not altered by treatment with PTX. Therefore, PTX dissociated the increased concentrations of cGMP from the ANF-mediated depression of evoked catecholamine release. C-ANF also dissociated elevations in cGMP concentrations from an ANF-mediated attenuation of evoked catecholamine release. The results of this study indicate that ANF inhibits adrenergic neurotransmission independent of guanylate cyclase.
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PMID:Neuromodulatory effects of atrial natriuretic factor are independent of guanylate cyclase in adrenergic neuronal pheochromocytoma cells. 197 29

Vasoactive intestinal polypeptide (VIP) was incubated in an adenylate cyclase assay with a particulate fraction of caudate-putamen (CP) tissue of the rat in order to examine the effect of the peptide on forskolin-activated adenylate cyclase in vitro. Forskolin induced an enhancement of cyclic AMP formation that was mediated by an effect on catalytic subunit and stimulatory guanine nucleotide regulatory protein (Ns). In our preparation, VIP did not influence basal adenylate cyclase activity or the stimulation by dopamine and sodium fluoride but, in the absence of guanylylimidodiphosphate (guanosine 5'-(beta, y-imido)-triphosphate) VIP inhibited the forskolin-stimulation of the enzyme in a noncompetitive manner. Met-encephalin, acting on a D-2 receptor-coupled putative inhibitory guanine nucleotide regulatory protein (Ni), inhibited the adenylate cyclase activity stimulated by forskolin to a slightly greater extent than VIP. When assayed together, these inhibition effects were additive, implying that the peptide receptors are not identical. The Ni-antagonist, MnCl2 completely blocked the inhibition of met-encephalin but had no significant effect on VIP-induced inhibition. In addition, pertussis toxin did not influence the effect of VIP on forskolin-stimulation in contrast to cholera toxin which did antagonize the VIP effect via the stimulatory guanine nucleotide regulatory protein (Ns). Furthermore, specific D-1 and D-2 dopaminergic receptor antagonists alpha(+)-flupentixol and spiperone had no effect on VIP-modulated forskolin-stimulated adenylate cyclase activity. These results suggest that the neuromodulatory effect of VIP is mediated by a Ns distinct from those involved in several adenylate cyclase pools sensitive to stimulation by dopamine and VIP in the rat striatum.
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PMID:The effect of vasoactive intestinal polypeptide (VIP) on forskolin stimulated adenylate cyclase in the caudate-putamen of the rat. 232 84

Vasoactive intestinal polypeptide (VIP) caused a reversible increase in the firing rate of locus coeruleus (LC) neurons. Voltage-clamp at -60 mV revealed that VIP induced an inward current associated with a small increase in conductance. The inward current persisted in the presence of Co2+ (to block Ca2+ channels) or tetrodotoxin (to block fast voltage-dependent Na+ channels). Substitution (80%) of Na+ with choline or Tris reduced the VIP-elicited inward current by approximately 75%. Changing external K+ concentrations did not alter the effect of VIP. The inward current induced by VIP became irreversible after the intracellular administration of GTP gamma S, a hydrolysis-resistant analog of GTP which can cause a prolonged activation of G-proteins. The intracellular application of GDP beta S, which can interfere with G-protein activation, attenuated the effect of VIP. Pertussis toxin, an inactivator of certain G-proteins, did not block the effect of VIP. We conclude that VIP directly excites LC neurons by inducing a largely Na-dependent inward current. As this effect became irreversible in the presence of intracellular GTP gamma S, was attenuated by GDP beta S, and was not eliminated by pertussis toxin, mediation through a pertussis toxin-insensitive G-protein is suggested.
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PMID:Excitation of locus coeruleus neurons by vasoactive intestinal peptide: evidence for a G-protein-mediated inward current. 251 5

Neuropeptide Y (NPY) regulation of intracellular cyclic AMP accumulation was studied in human Ewing's sarcoma cell line, WE-68. NPY inhibited vasoactive intestinal peptide (VIP)- and dopamine-stimulated but not basal cyclic AMP formation. The peptide effect was rapid (less than 2 min), concentration-dependent with a half-maximal effective concentration (EC50) of 8 nM NPY, and maximal inhibition reaching 60-70% with 100 nM NPY. Prior exposure of WE-68 cells to pertussis toxin completely abolished the inhibitory action of NPY. It is concluded that NPY attenuates agonist-stimulated cyclic AMP formation in Ewing's sarcoma WE-68 cells, and may do so via the inhibitory guanine nucleotide regulatory protein of adenylate cyclase.
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PMID:Neuropeptide Y inhibits vasoactive intestinal peptide- and dopamine-induced cyclic AMP formation in human Ewing's sarcoma WE-68 cells. 254 51

Different peptide hormones influence hormone secretion in pituitary cells by diverse second messenger systems. Recent data indicate that luteinizing-hormone-releasing hormone (LHRH) stimulates and somatostatin inhibits voltage-dependent Ca2+ channels of GH3 cells via pertussis-toxin-sensitive mechanisms [Rosenthal et al. (1988) EMBO J. 7, 1627-1633]. In other pituitary cell lines, somatostatin has been shown to cause a pertussis-toxin-sensitive decrease in adenylate cyclase activity, and LHRH and thyrotropin-releasing hormone (TRH) stimulate phosphoinositol lipid hydrolysis in a pertussis-toxin-independent manner. Whether stimulation of Ca2+ influx by TRH is affected by pertussis toxin is not known. In order to elucidate which of the hormone receptors interact with pertussis-toxin-sensitive and -insensitive G-proteins, we measured the effects of LHRH, somatostatin and TRH on high-affinity GTPases in membranes of GH3 cells. In control membranes, both LHRH and TRH stimulated the high-affinity GTPase by 20%, somatostatin by 25%. Maximal hormone effects were observed at a concentration of about 1 microM. Pretreatment of cells with pertussis toxin abolished pertussis-toxin-catalyzed [32P]ADP-ribosylation of 39-40-kDa proteins in subsequently prepared membranes and reduced basal GTPase activity. The toxin also reduced by more than half the increases in GTPase activity induced by LHRH and TRH; stimulation of GTPase by somatostatin was completely suppressed. Stimulation of adenylate cyclase by vasoactive intestinal peptide (VIP) was not impaired by pretreatment of cells with pertussis toxin. Somatostatin but not LHRH and TRH decreased forskolin-stimulated adenylate cyclase activity. The results suggest that the activated receptors for LHRH and TRH act via pertussis-toxin-sensitive and -insensitive G-proteins, whereas effects of somatostatin are exclusively mediated by pertussis-toxin-sensitive G-proteins.
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PMID:Secretion-stimulating and secretion-inhibiting hormones stimulate high-affinity pertussis-toxin-sensitive GTPases in membranes of a pituitary cell line. 256 42

The effects of two hormones, vasopressin and somatostatin (SOM), on ion secretion in rat colon descendens were compared. Three modes for induction of epithelial secretion were used: neuronally mediated secretion due to electric field stimulation (EFS), Ca2+-dependent secretion elicited by carbachol, and cAMP-dependent secretion evoked either by a receptor-mediated mechanism elicited by vasoactive intestinal peptide (VIP) or by a direct activation of the adenylate cyclase by means of forskolin. Somatostatin inhibited ion secretion evoked by EFS (55-65%), carbachol (80%) and VIP (95%) in a dose-dependent manner. Maximal inhibition by SOM was observed at 10(-7) M. Somatostatin had, however, no effect on the secretory response to forskolin. The inhibition of the VIP effect could be attenuated by pretreatment with pertussis toxin. In contrast, vasopressin in concentrations as low as 0.025-0.25 U/liter decreased the secretory effects of EFS (55-75%) and carbachol (85%), but had no effect on cAMP-dependent secretion elicited either by VIP or forskolin. The results suggest that the antisecretory effect of vasopressin is mediated only by a block in the Ca2+ pathway, whereas SOM inhibits Ca2+-dependent secretion as well as receptor-mediated cAMP-dependent secretion. The interaction with the cAMP pathway is located at the step between stimulation of the receptor and activation of the adenylate cyclase and probably involves an Ni-protein.
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PMID:Antisecretory effects of somatostatin and vasopressin in the rat colon descendens in vitro. 256 91

We examined the mechanism by which adenosine inhibits prolactin secretion from GH3 cells, a rat pituitary tumour line. Prolactin release is enhanced by vasoactive intestinal peptide (VIP), which increases cyclic AMP, and by thyrotropin-releasing hormone (TRH), which increases inositol phosphates (IPx). Analogues of adenosine decreased prolactin release, VIP-stimulated cyclic AMP accumulation and TRH-stimulated inositol phospholipid hydrolysis and IPx generation. Inhibition of InsP3 production by R-N6-phenylisopropyladenosine (R-PIA) was rapid (15 s) and was not affected by the addition of forskolin or the removal of external Ca2+. Addition of adenosine deaminase or the potent adenosine-receptor antagonist, BW-A1433U, enhanced the accumulation of cyclic AMP by VIP, indicating that endogenously produced adenosine tonically inhibits adenylate cyclase. The potency order of adenosine analogues for inhibition of cyclic AMP and IPx responses (measured in the presence of adenosine deaminase) was N6-cyclopentyladenosine greater than R-PIA greater than 5'-N-ethylcarboxamidoadenosine. This rank order indicates that inhibitions of both cyclic AMP and InsP3 production are mediated by adenosine A1 receptors. Responses to R-PIA were blocked by BW-A1433U (1 microM) or by pretreatment of cells with pertussis toxin. A greater amount of toxin was required to eliminate the effect of R-PIA on inositol phosphate than on cyclic AMP accumulation. These data indicate that adenosine, in addition to inhibiting cyclic AMP accumulation, decreases IPx production in GH3 cells, possibly by directly inhibiting phosphoinositide hydrolysis.
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PMID:Regulation of GH3-cell function via adenosine A1 receptors. Inhibition of prolactin release, cyclic AMP production and inositol phosphate generation. 284 12

The neuropeptide somatostatin inhibits hormone release from GH4C1 pituitary cells via two mechanisms: inhibition of stimulated adenylate cyclase and a cAMP-independent process. To determine whether both mechanisms involve the guanyl nucleotide-binding protein Ni, we used pertussis toxin, which ADP-ribosylates Ni and thereby blocks its function. Pertussis toxin treatment of GH4C1 cells blocked somatostatin inhibition of both vasoactive intestinal peptide (VIP)-stimulated cAMP accumulation and prolactin secretion. In membranes prepared from toxin-treated cells, somatostatin inhibition of VIP-stimulated adenylate cyclase activity was reduced and 125I-Tyr1-somatostatin binding was decreased more than 95%. In contrast, pertussis toxin did not affect the biological actions or the membrane binding of thyrotropin-releasing hormone. These results indicate that ADP-ribosylated Ni cannot interact with occupied somatostatin receptors and that somatostatin inhibits VIP-stimulated adenylate cyclase via Ni. To investigate somatostatin's cAMP-independent mechanism, we used depolarizing concentrations of K+ to stimulate prolactin release without altering intracellular cAMP levels. Measurement of Quin-2 fluorescence showed that 11 mM K+ increased intracellular [Ca2+] within 5 s. Somatostatin caused an immediate, but transient, decrease in both basal and K+-elevated [Ca2+]. Consistent with these findings, somatostatin inhibited K+-stimulated prolactin release, also without affecting intracellular cAMP concentrations. Pertussis toxin blocked the somatostatin-induced reduction of [Ca2+]. Furthermore, the toxin antagonized somatostatin inhibition of K+-stimulated and VIP-stimulated secretion with the same potency (ED50 = 0.3 ng/ml). These results indicate that pertussis toxin acts at a common site to prevent somatostatin inhibition of both Ca2+- and cAMP-stimulated hormone release. Thus, Ni appears to be required for somatostatin to decrease both cAMP production and [Ca2+] and to inhibit the actions of secretagogues using either of these intracellular messengers.
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PMID:Pertussis toxin blocks both cyclic AMP-mediated and cyclic AMP-independent actions of somatostatin. Evidence for coupling of Ni to decreases in intracellular free calcium. 286 57


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