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)

To clarify the role of the breakdown of phosphatidylinositol 4,5-bisphosphate (PIP2) in GH secretion in human somatotrophs and the effects of inhibitors of GH secretion on this mechanism, we studied the effects of 12-tetradecanoylphorbol-13-acetate (TPA) and phospholipase C (Plase C) on GH secretion and the interactions of somatostatin (SRIH), bromocriptine, and pertussis toxin (IAP) with TPA or Plase C, using human GH-secreting pituitary adenoma cells in culture. SRIH (10(-9)-10(-7) M) inhibited and TPA (10(-10)-10(-8) M) and Plase C (0.125-1.0 U/mL) stimulated GH secretion. SRIH (10(-9)-10(-7) M) inhibited GH release induced by TPA (10(-8) M) or Plase C (1.0 U/mL). Bromocriptine (10(-8) M) also inhibited 10(-8) M TPA-induced GH secretion. When adenoma cells were treated with 100 ng/mL IAP for 24 h, basal and TPA-induced GH secretion rates did not change. However, the inhibitory effects of SRIH (10(-8) M) or bromocriptine (10(-8) M) on basal and 10(-8) M TPA-stimulated GH secretion were attenuated. In addition, IAP reduced GH secretion induced by 0.5 U/mL Plase C, while SRIH inhibition of Plase C-evoked GH release was diminished by IAP. We conclude that the hydrolysis of PIP2 by Plase C, which causes activation of protein kinase C by 1,2-diacylglycerol and Ca2+ mobilization by inositol 1,4,5-triphosphate, is a physiological intracellular mechanism leading to GH secretion in human somatotrophs; SRIH inhibits GH secretion mediated by this mechanism, and bromocriptine blocks at least protein kinase C-mediated GH release; the inhibitory guanine nucleotide-binding protein (Ni) is involved in these inhibitory effects of SRIH and bromocriptine; and Ni modulates the breakdown of PIP2 by Plase C.
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PMID:Phorbol ester and phospholipase C-induced growth hormone secretion from pituitary somatotroph adenoma cells in culture: effects of somatostatin, bromocriptine, and pertussis toxin. 288 Aug 63

In mammalian cardiac muscle, muscarinic and adenosine receptors serve as inhibitory physiological modulators of myocardial functions. Dual inhibitory regulation of myocardial function via stimulation of these receptors is established through cyclic AMP-dependent and cyclic AMP-independent subcellular processes. The inhibitory signals triggered by agonist binding to the respective receptors are transmitted to the subsequent biochemical, electrophysiological and functional changes through activation of the GTP-binding proteins, Ni and/or N0, which couple the signal at binding sites to the catalytic subunit of adenylate cyclase in the actions mediated through the cyclic AMP-dependent mechanism, or to potassium channels in those mediated by cyclic AMP-independent processes preferentially exerted in atrial and SA nodal cells. The functional role of polyphosphoinositide breakdown promoted by muscarinic receptor activation in myocardium has not been elucidated. IAP (islet-activating protein, pertussis toxin) is capable of uncoupling the receptor stimulation to activation of Ni and/or N0, thus resulting in the inhibition of negative inotropic and chronotropic responses to muscarinic receptor agonists, and to adenosine and its derivatives such as N6-phenylisopropyladenosine and N6-methyladenosine. Both the cyclic AMP-dependent and cyclic AMP-independent inhibitory mechanisms are susceptible to IAP.
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PMID:[Adenosine and muscarinic receptors in regulation of myocardial contractility: dual mechanism of inhibitory action]. 289 52

Islet-activating protein (IAP, a Bordetella pertussis toxin) was employed to test the hypothesis that the inhibitory GTP-binding regulatory protein of adenylate cyclase (Ni) mediates GTP effects on the binding of Ca2+-mobilizing hormones to liver plasma membranes and is involved in calcium mobilization stimulated by these agonists. IAP added to normal liver plasma membranes catalyzed the incorporation of radioactivity from [32P]NAD into a 41,000-Da peptide (presumably the alpha-subunit of Ni). However, no such incorporation was observed in liver membranes prepared from rats 24 hr after intraperitoneal injection of IAP. Angiotensin II attenuated glucagon-stimulated increases in cAMP in hepatocytes prepared from control but not IAP-treated rats. In contrast, following IAP treatment, no changes were observed in the ability of glucagon, vasopressin, angiotensin II, or epinephrine to activate phosphorylase; nor did this treatment alter [3H]vasopressin binding or epinephrine displacement of [3H]prazosin binding. However, IAP treatment decreased [3H]angiotensin II binding affinity when studies were performed in the absence but not the presence of 5'-guanylylimidodiphosphate (GppNHp). This shift was small and represented only 5-8% of the shift in apparent Kd elicited by GppNHp in untreated membranes. In vitro studies with IAP confirmed the results of the radioligand binding studies using in vivo IAP treatment. The effects of NaCl on [3H]angiotensin II binding were also tested but were not typical of other receptors which couple to Ni. The data suggest that, although a small population of hepatic angiotensin II receptors couple to Ni and attenuate glucagon-stimulated increases in cAMP, vasopressin, alpha 1-adrenergic, and the majority of angiotensin II receptors do not interact significantly with Ni. Thus, although there is evidence that agonist-induced Ca2+ mobilization requires a GTP-binding regulatory protein, this protein does not appear to be Ni in rat liver.
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PMID:Effect of islet-activating pertussis toxin on the binding characteristics of Ca2+-mobilizing hormones and on agonist activation of phosphorylase in hepatocytes. 300 28

Opioid tolerance and dependence are characterized in terms of inhibitory and excitatory neuronal mechanisms. Bacterial toxins were used to investigate these phenomena in the isolated guinea-pig ileum (GPI) and mouse vas deferens (MVD). Cholera toxin (CT) and pertussis toxin (islet activating protein; IAP) have been demonstrated to selectively impair the function of either the stimulatory or inhibitory nucleotide regulatory protein, mediating the signal transmission to the adenylate cyclase. It has been found that CT failed to affect electrically evoked twitch tension in naive and tolerant GPI and MVD. Twitch tension evoked by excitatory drugs, e.g. neurotensin, was attenuated in the GPI, but not in the MVD. CT did not interfere with the actions of opioids or nonopioids in either the GPI or the MVD. Similarly, IAP failed to affect electrically evoked twitch tension. It virtually lacked an effect on the inhibitory action of opioids and nonopioids on electrically stimulated naive and tolerant GPI and MVD. On the other hand, both CT and IAP dose-dependently attenuated the naloxone precipitated withdrawal contracture in the GPI rendered opioid-dependent. These findings may suggest that opioid receptors at nerve terminals of the GPI and the MVD are not linked to adenylate cyclase, and those receptors relate to the state of tolerance. In contrast, opioid receptors located at nerve somata may be linked to adenylate cyclase. Those receptors may be associated with the development of dependence. The experiments with CT suggest a synaptic excitatory input of neighboring nerve elements necessary for the generation of a withdrawal contracture.
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PMID:Effect of cholera toxin and pertussis toxin on opioid tolerance and dependence in the guinea-pig myenteric plexus. 301 78

In an attempt to identify the nature of guanine nucleotide binding protein(s) (G-protein) involved in the acetylcholine (ACh)-induced (muscarinic) response of pig coronary-artery smooth muscle, we studied the effect of ADP-ribosylation of specific membrane protein(s) catalysed by islet-activating protein (IAP; pertussis toxin). The ACh-stimulated and guanine nucleotide-dependent activities of phosphatidylinositol 4,5-bisphosphate (PIP2) phosphodiesterase (PDE), assessed by the production of inositol 1,4,5-trisphosphate (IP3) from exogenously applied PIP2, were not modified, in either IAP-treated or non-treated cell homogenates used as the enzyme source. In intact tissues, pretreatment with up to 100 ng of IAP/ml inhibited neither the ACh-induced decrease in the amount of inositol phospholipids nor the increase in the amounts of phosphatidic acid and of inositol phosphates. IAP treatment increased the amount of cyclic AMP accumulated by isoprenaline. These observations suggest that G-protein which couples the muscarinic receptor to PIP2-PDE is insensitive to IAP. Such being the case, the nature of this protein(s) probably differs from that required for the regulation of adenylate cyclase activities (Ni or Gi).
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PMID:Guanine nucleotide binding protein involved in muscarinic responses in the pig coronary artery is insensitive to islet-activating protein. 303 Feb 65

Possible coupling of bovine adrenal medullary opioid receptors to islet-activating protein (IAP, pertussis toxin)-sensitive GTP-binding proteins was investigated by studying effects of guanyl-5'-yl imidodiphosphate (Gpp(NH)p) and IAP treatment of membranes on opioid binding. Gpp(NH)p inhibited [3H]D-Ala2-D-Leu5-enkephalin ([3H]DADLE) binding by increasing the dissociation constant of [3H]DADLE and membranes, and enhanced slightly [3H]diprenorphine binding. IAP treatment of membranes reduced [3H]DADLE binding and abolished almost completely the Gpp(NH)p inhibition of [3H]DADLE binding. Treatment of membranes with IAP and [32P]NAD resulted in radio-labeling of membrane proteins of approximately 39,000 dalton. DADLE inhibited adenylate cyclase activity in rat brain caudate nucleus. However, DADLE, beta-endorphin, levorphanol and dynorphin A(1-13) did not show any significant inhibitory action on bovine adrenal medullary adenylate cyclase activity. These results suggest that bovine adrenal medullary opioid (DADLE) receptors are linked to IAP-sensitive GTP-binding proteins which are not directly coupled to adenylate cyclase.
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PMID:Coupling of adrenal medullary opioid receptors to islet-activating protein-sensitive GTP-binding proteins. 303 14

Cholera toxin (CT) and islet-activating protein (IAP, a Bordetella pertussis toxin) were employed to test the hypothesis that GTP-binding regulatory proteins are released from plasma membranes to a greater extent when 'activated' than when 'inactivated'. CT, which activates Ns (the stimulatory GTP-binding regulatory protein of the adenylate cyclase system), catalyzed the incorporation of radioactivity from [32P]NAD into 45 and 47.5 kDa peptides associated with rat liver plasma membranes. Following ADP-ribosylation and centrifugation at 100000 X g for 1 h, approx. 30-35% of these CT-labelled peptides were no longer associated with the plasma membranes, but were recovered from the supernatant fraction. IAP, which inactivates Ni (the inhibitory GTP-binding regulatory protein of the adenylate cyclase system) catalyzed the incorporation of radioactivity from [32P]NAD into a 41 kDa peptide associated with the membranes. However, in contrast to the CT-labelled peptides, typically less than 5% of the IAP-labelled peptide was found in the 100000 X g supernatant fraction, but rather was almost exclusively associated with the membrane pellet. The data indicate that the alpha-subunits of Ns are released from the plasma membrane following activation, and support the hypothesis that the beta gamma-subunits act to anchor the alpha-subunits to the plasma membrane.
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PMID:Alpha-subunits of Ns are released from the plasma membrane following cholera toxin activation. 308 21

The coupling of muscarinic receptors with G-proteins was investigated in cultured myocytes prepared from the hearts of newborn rats. The coupling was investigated in both young (5 days after plating) and aged (14 days after plating) cultures, in view of the completely different effects of 5'-guanylyl imidodiphosphate [Gpp(NH)p] on muscarinic agonist binding to homogenates from young vs aged cultures [Moscona-Amir, E., Henis, Y. I., Yechiel, E., Barenholz, Y., & Sokolovsky, M. (1986) Biochemistry 25, 8118-8124]. Pretreatment of cultures from both ages by Bordetella pertussis toxin (IAP) was found to eliminate any Gpp(NH)p effect on carbamylcholine binding. IAP by itself induced a rightward shift in the carbamylcholine competition curve in homogenates from aged cultures, but no such effect was observed in homogenates from young cultures. IAP-catalyzed [32P]ADP-ribosylation of membrane preparations from young and aged cultures revealed major differences between them. Young cultures exhibited a major IAP substrate at 40 kDa, which was also recognized by anti-alpha i antibodies, and two novel IAP substrates at 28 and 42 kDa, which were weakly ADP-ribosylated by the toxin and were not recognized with either anti-alpha i or anti-alpha o antibodies. In aged cultures, only the 40-kDa band (ribosylated to a lower degree) was detected. The parallel age-dependent changes in the three IAP substrates (28, 40, and 42 kDa) and in the interactions of the G-protein(s) with the muscarinic receptors strongly suggest close association between the two phenomena. All of these age-dependent changes in the G-protein related parameters were prevented by phosphatidylcholine-liposome treatment of the aged cultures.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Guanosine 5'-triphosphate binding protein (Gi) and two additional pertussis toxin substrates associated with muscarinic receptors in rat heart myocytes: characterization and age dependency. 313 31

The control of M-current by muscarinic ACh receptors and luteinizing hormone releasing hormone (LHRH) receptors was studied in dialyzed frog sympathetic ganglion neurons. M-current was recorded in dialyzed cells without run-down or changes in its biophysical properties and could be reversibly suppressed by muscarine and teleost LHRH (t-LHRH). However, dialysis with internal solutions lacking ATP or substituting with APP(NH)P caused the loss of M-current, suggesting that dephosphorylation suppresses the activity of M-channels. M-current over-recovers after agonist addition and removal to a size 30% larger than control, as if latent channels are activated during the recovery. Dialysis of cells with the G-protein activators GTP gamma S, fluoride, and aluminum fluoride causes loss of M-current. G-protein activation by receptors was confirmed by dialysis with low concentrations of GTP gamma S in competition with GTP. This prevents the rapid loss of M-current, but addition of muscarine or t-LHRH caused irreversible loss of M-current, suggesting that both transmitter receptors do suppress M-current by activating a G-protein. Suppression of M-current was not affected by treatment with 0.1 microgram/ml pertussis toxin (IAP) for 24-48 hr. In addition, based on the lack of IAP-specific labeling of frog sympathetic neuron membrane proteins, no IAP-sensitive G-proteins are present in these cells. These results indicate that an IAP-insensitive G-protein couples muscarinic and LHRH receptors to the suppression of M-current.
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PMID:Muscarine and t-LHRH suppress M-current by activating an IAP-insensitive G-protein. 313 47

Exocytosis was studied in single rat peritoneal mast cells. Granule fusion was monitored by time-resolved capacitance measurements using the patch-clamp technique. Intracellular stimulation of mast cells with 20 microM GTP-gamma-S stimulates exocytosis with a calcium-dependent time course. Secretion in response to receptor-mediated stimulation with compound 48/80 was completely abolished by treatment with pertussis toxin (IAP) at 180 ng/ml for 4 h. The time course of exocytosis in response to GTP-gamma-S remained unaffected in IAP-treated cells supporting the involvement of a second GTP-binding protein in stimulus-secretion coupling.
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PMID:Pertussis toxin does not affect the time course of exocytosis in mast cells stimulated by intracellular application of GTP-gamma-S. 330 15


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