Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adenylyl cyclase in rat adipose cells is stimulated by ligands for Rs receptors (e.g. isoproterenol) and inhibited by ligands for Ri receptors (e.g. adenosine). In contrast, Rs receptors mediate inhibition and Ri receptors mediate augmentation of insulin-stimulated glucose transport activity by a process independent of changes in cellular cAMP-dependent protein kinase activity [Kuroda M., Honnor R. C., Cushman S. W., Londos C. and Simpson I. A. (1987) J. biol. Chem. 262, 245-253]. The present study examines the possible role of G-proteins in the regulation of insulin-stimulated glucose transport activity by Rs and Ri receptors. First, conditions were established that permit intoxication of isolated rat adipocytes by cholera and pertussis toxins without compromising cell integrity. Effectiveness of toxin treatment was monitored by examining adenylyl cyclase activity in isolated plasma membranes. Secondly, neither toxin interfered with the ability of a maximal concentration insulin to initiate the glucose transport response. Thirdly, pertussis toxin eliminated the augmenting effects of adenosine on insulin-stimulated glucose transport activity, but enhanced the inhibitory effects of isoproterenol. Findings with ligands for other Ri receptors (nicotinic acid and prostaglandin E2) mirrored those with adenosine. Finally, cholera toxin elicited a modest depression of transport activity, and only in the absence of an Ri ligand (e.g. adenosine). Furthermore, in contrast to the enhanced stimulation of adenylyl cyclase by isoproterenol and GTP, cholera toxin eliminated the inhibitory effect of isoproterenol on transport activity. The augmentative effects of adenosine on transport activity were unchanged. Measurements of (-/+cAMP) cAMP-dependent protein kinase activity ratios reinforce the notion that modulation of glucose transport activity is independent of changes in cAMP. We conclude that regulation of glucose transport activity by Rs and Ri receptors is mediated by the G-proteins, Gs and Gi (or other toxin substrates), respectively. Inasmuch as such regulation occurs at the plasma membrane and appears to be cAMP-independent, it is suggested that glucose transporters may be direct targets for receptor: G-protein interactions.
 ...
PMID:Cholera and pertussis toxins modify regulation of glucose transport activity in rat adipose cells: evidence for mediation of a cAMP-independent process by G-proteins. 131 47

A prototypic Ca(2+)-mobilizing hormone receptor, alpha 1-adrenergic receptor (alpha 1AR), stimulates cAMP accumulation. The mechanism underlying this phenomenon was previously suggested to be secondary to phosphatidylinositol hydrolysis-protein kinase C activation in some cells. We transfected Chinese hamster ovary (CHO)-K1 cells with hamster alpha(1B)AR cDNA and isolated cells stably expressing alpha(1B)AR (CHO alpha 1B cells). We investigated the molecular mechanism underlying the alpha 1AR-mediated cAMP production in the CHO alpha 1B cells. Norepinephrine (NE) stimulated intracellular calcium mobilization and cAMP production through alpha(1B)AR. Pretreatment with a phospholipase C inhibitor, U-73,122 (10 microM), abolished the NE-induced intracellular calcium response, whereas it did not affect the NE-stimulated cAMP production. Treatment with various agents (protein kinase C inhibitors, calcium ionophore, cyclo-oxygenase inhibitor, or pertussis toxin) had little effect on the NE-induced cAMP production. The parent CHO and CHO alpha 1B cells contained similar amounts of Gs alpha (42 and 45 kDa, respectively), as detected with immunoblot analysis, and exhibited similar extents of cAMP synthesis with cholera toxin and forskolin. Adenylyl cyclase activity in the CHO alpha 1B cell membranes was also enhanced by NE. Furthermore, incubation of CHO alpha 1B cell membranes with antiserum directed against the carboxyl-terminal portion of Gs alpha inhibited the NE-stimulated adenylyl cyclase activity. Taken together, the results indicate that the alpha(1B)AR-mediated cAMP synthesis in CHO alpha 1B cells reflects direct stimulation of Gs-adenylyl cyclase. Therefore, the alpha 1AR-stimulated cAMP production observed in some native tissues may involve the multiple mechanisms of the direct activation of Gs-adenylyl cyclase and a secondary effect through activation of phosphatidylinositol hydrolysis.
 ...
PMID:Hamster alpha 1B-adrenergic receptor directly activates Gs in the transfected Chinese hamster ovary cells. 756 18

The presence of large numbers of dopaminergic neurons in the olfactory bulb suggests that dopamine plays an important role in olfaction. Dopamine D2 receptors are produced in olfactory sensory neurons [Shipley et al. (1991) Chem. Senses 16, 5] and found in relatively high concentrations in their terminals in the nerve and glomerular layers of the olfactory bulb [Nickell et al. (1991) NeuroReport 2, 9-12]. In other systems D2 receptors are linked to adenylyl cyclase by an inhibitory G-protein, and activation of the receptors results in inhibition of the enzyme. We examined rat olfactory mucous membrane to determine whether the D2 receptors were linked functionally to adenylyl cyclase as they are in other tissues. Adenylyl cyclase is found in both the olfactory cilia of the sensory epithelium and olfactory nerve terminals in the bulb. Bromocriptine, a D2 receptor agonist, was added to olfactory epithelium membrane preparations from normal and unilaterally bulbectomized adult rats and the preparations were assayed for forskolin-stimulated adenylyl cyclase activity. In unoperated animals bromocriptine significantly inhibited adenylyl cyclase activity, and the inhibition was abolished following pertussis toxin treatment. In mucosa from unilaterally bulbectomized animals we saw significantly lower adenylyl cyclase activity on the operated side and a further decrease in response to bromocriptine. The data indicate that bromocriptine decreases adenylyl cyclase activity in olfactory tissue, specifically in the sensory neurons, and the reaction is dependent on a pertussis toxin-sensitive G-protein.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Bromocriptine, a dopamine D2 receptor agonist, inhibits adenylyl cyclase activity in rat olfactory epithelium. 790 56

The loss of the ability in signalling transduction constitutes an attractive hypothesis to explain the age-related loss of functions in the nervous system. In this paper we have examined adenylyl cyclase and G proteins in Ceratitis capitata brain during aging. The intermediate level of complexity of the Mediterranean fruit fly and its short lifespan make it a particularly interesting system for aging studies. Adenylyl cyclase basal activity decreased in the course of aging. By contrast, neither guanine nucleotide-induced activation of adenylyl cyclase nor Gs protein levels were modified. However, adenylyl cyclase activation by octopamine, which is a major neurotransmitter, neuromodulator and neurohormone in insects, was lost during aging. This observation correlated with a decrease in octopamine binding to brain plasma membranes that was due to a decrease in both receptor affinity and binding sites. On the other hand, we observed an increase in the expression of C. capitata Go protein with age, as revealed by pertussis toxin-catalysed ADP-ribosylation and immunoblotting experiments, that was not correlated with an increase in beta subunit levels. This report constitutes the first direct evidence for the participation of a Go protein in aging in the nervous system.
 ...
PMID:Octopamine-sensitive adenylyl cyclase and G proteins in Ceratitis capitata brain during aging. 793 99

The interaction of beta 1- and beta 3-adrenergic receptors and G(i) proteins was examined in rat adipocytes. In intact adipocytes, cyclic AMP accumulation stimulated by the beta 3-selective agonist, BRL 37344 (BRL), was potentiated by pertussis toxin (PTX), as was the beta 1-sensitive component of isoproterenol (ISO)-stimulated cyclic AMP accumulation. These data suggest that beta 1 and beta 3-receptors interact with both Gs and G(i) in intact adipocytes. Further analysis of the activation of adenylyl cyclase by the beta-receptor subtypes was performed in adipocyte membranes in which the activity of G(i) was manipulated by both GTP and PTX. Unlike cyclic AMP accumulation in cells, the activation of membrane adenylyl cyclase by ISO could be clearly resolved into components mediated by beta 1-(high affinity) or beta 3-(low affinity) receptors. The beta 3-receptor-mediated activity was dramatically reduced at 0.1 mM GTP compared to 0.1 microM GTP, but the activity mediated by beta 3-receptors was significantly reduced at concentrations of GTP in which G(i) proteins are active. Adenylyl cyclase activity stimulated by BRL was also inhibited at high concentrations of GTP. PTX abolished the inhibition of beta 3-receptor-stimulated activity by high GTP concentrations. This is the first study to indicate that G(i) proteins can limit beta 3- but not beta 1-stimulated adenylyl cyclase activity and are consistent with the hypothesis that beta 3-receptors interact with both Gs and G(i), whereas beta 1-receptors couple predominantly to Gs.
 ...
PMID:Differential interaction of beta 1- and beta 3-adrenergic receptors with Gi in rat adipocytes. 794 69

Many important airway epithelial cell functions are regulated by intracellular cAMP. Adenylyl cyclase, the enzyme that synthesizes cAMP, is under dual regulation in many cells, but muscarinic agonists have not been shown to inhibit adenylyl cyclase in human and dog epithelial cells, despite the presence of muscarinic receptors. We question whether the lack of inhibition was related to the absence of a component of the inhibitory pathway or a lack of coupling between the components. The GTP-binding regulatory proteins (G proteins) that regulate adenylyl cyclase activity in airway epithelium have not been well characterized. We used primary cultures of guinea pig tracheal epithelial cells as a model system and identified the G proteins that modulate adenylyl cyclase activity. Immunoblot analysis demonstrated the presence of alpha subunits corresponding to stimulatory (Gs alpha) and inhibitory [Gi alpha (2) and Gi alpha (3)] G proteins as well as beta chains. These G proteins were functionally coupled to stimulation and inhibition of adenylyl cyclase in epithelial membrane preparations. Pertussis toxin-catalyzed [32P]ADP-ribosylation of Gi alpha was significantly reduced by 100 microM GTP gamma S (78.4 +/- 3.6% of control), by 100 mM NaF (41.9 +/- 9.1% of control), and by carbachol (100 microM) (29.2 +/- 9.0% of control). Atropine (10 microM) inhibited the carbachol effect by greater than 90%, suggesting that the muscarinic receptors were functionally coupled to Gi proteins. beta-Adrenergic agonists increased adenylyl cyclase activity, but muscarinic agonists failed to inhibit this enzyme. In summary, guinea pig tracheal epithelial membranes contain muscarinic receptors, Gi alpha (2) and adenylyl cyclase, which are appropriately coupled.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Characterization of GTP-binding proteins coupled to inhibition of adenylyl cyclase in guinea pig tracheal epithelial cells. 800 43

Muscarinic m4 acetylcholine receptors are normally coupled through Gi to inhibition of adenylyl cyclases. In the olfactory bulb and some cultured cells, however, m4 receptors can couple to stimulation of adenylyl cyclase activity. In this study, m4 receptors and specific isozymes of adenylyl cyclases were coexpressed in HEK-293 cells to characterize the mechanism(s) for m4 receptor stimulation of adenylyl cyclases. The calmodulin-sensitive type I and type III adenylyl cyclases were chosen for this study because neither enzyme is stimulated by the beta/gamma complex of G coupling proteins. M4 receptors exhibited either inhibition or stimulation of type I and III adenylyl cyclases depending upon receptor density and agonist concentration. Inhibition of adenylyl cyclase was apparently due to M4 coupling through Gi. Adenylyl cyclase stimulation through m4 receptors was not due to increases in intracellular Ca2+ and stimulation of the calmodulin-sensitive enzymes since it was evident in isolated membranes in the absence of free Ca2+ and with whole cells preloaded with the Ca2+ chelator BAPTA/AM. Stimulation of adenylyl cyclase activities by m4 receptors was apparently mediated via Gs since it was GTP-dependent, was insensitive to pertussis toxin, and was not due to beta/gamma stimulation. Synthetic peptides derived from a G protein activating region of the m4 receptor mimicked the m4-mediated stimulation of adenylyl cyclase activity. These data demonstrate a novel mechanism for muscarinic regulation of adenylyl cyclases that may involve crossover from inhibitory to stimulatory G protein coupling.
 ...
PMID:A novel mechanism for coupling of m4 muscarinic acetylcholine receptors to calmodulin-sensitive adenylyl cyclases: crossover from G protein-coupled inhibition to stimulation. 830 42

It has been known for some time that chronic treatment of neuronal cells and tissues with opioids, contrary to their acute effect, leads to an increase in cAMP accumulation. This phenomenon, defined as adenylyl cyclase superactivation, has been implicated in opiate addiction, yet the mechanism by which it is induced remains unclear. Here, we show that this phenomenon can be reproduced and studied in COS-7 cells cotransfected with adenylyl cyclase type V and mu-opioid receptor cDNAs. These cells display acute opioid inhibition of adenylyl cyclase activity, whereas prolonged exposure to the mu-agonist morphine or [-Ala2, N-methyl-Phe4, Gly-ol5]enkephalin leads to a time-dependent superactivation of adenylyl cyclase. This superactivated state is reversible, because it is gradually lost following agonist withdrawal. Adenylyl cyclase superactivation can be prevented by pertussis toxin pretreatment, indicating the involvement of Gi/o proteins, or by cotransfection with the carboxyl terminus of beta-adrenergic receptor kinase or with alpha-transducin (scavengers of Gbetagamma dimers), indicating a role for the G protein betagamma dimers in adenylyl cyclase superactivation. However, contrary to several other Gbetagamma-dependent signal transduction mechanisms (e.g. the extracellular signal-regulated kinase 2/MAP kinase pathway), adenylyl cyclase superactivation is not affected by the Ras dominant negative mutant N17-Ras.
 ...
PMID:Chronic opioid treatment induces adenylyl cyclase V superactivation. Involvement of Gbetagamma. 870 9

After long-lasting administration of estradiol (4-6 weeks) in the presence or absence of pertussis toxin treatment we followed up the changes in body weight and adenohypophyseal weight in rats subjected to this treatment. The most striking effect was the potentiating effect of pertussis toxin on the estradiol-induced adenohypophyseal growth reaction. Adenylyl cyclase activity in the adenohypophysis was significantly increased in the estradiol-treated group and the addition of pertussis toxin did not further increase this enzyme activity. The lipolytic activity in adipose tissue exhibited a similar response as adenohypophyseal growth. Adrenergic lipolysis stimulated by pertussis toxin was highly significantly increased in tissues of rats treated with pertussis toxin. Our results show that the estrogen-induced adenohypophyseal growth reaction is highly potentiated by the treatment of rats with pertussis toxin and that this effect is in many aspects similar to that observed in adrenergic lipolysis. It thus seems that both processes might be mediated via a pertussis toxin-sensitive G protein which is involved in inhibitory regulation of adenylyl cyclase.
 ...
PMID:Effects of pertussis toxin treatment of rats on estradiol-induced adenohypophyseal growth reaction and on adrenergic lipolysis. 879 76

Several agonists including norepinephrine, somatostatin, galanin, and prostaglandins inhibit insulin release. The inhibition is sensitive to pertussis toxin, indicating the involvement of heterotrimeric Gi and/or Go proteins. Receptors for the different agonists have different selectivity for these G proteins. After G protein activation, the alpha- and beta gamma-subunits dissociate and interact with multiple targets to inhibit release. These include 1) the ATP-sensitive K+ channel and perhaps other K+ channels, 2) L-type voltage-dependent Ca2+ channels, 3) adenylyl cyclase, and 4) a "distal" site late in stimulus-secretion coupling. The latter effect, which may be exerted close to the final stage of exocytosis, is the most powerful of the individual inhibitory mechanisms. G protein action on the target molecules is determined by the individual G proteins activated and their specificity for the targets. The L-type Ca2+ channel is inhibited by G(o)-1. Adenylyl cyclase is inhibited by Gi-2 and Gi-3. The distal inhibition can be exerted by Gi-1, Gi-2, Gi-3, and G(o)-2. Thus there is both selectivity and promiscuity in G protein action in the beta-cell. These characteristics allow an inhibitory ligand to be effective at multiple targets and to act differentially from other inhibitory ligands.
 ...
PMID:Mechanisms of inhibition of insulin release. 899 78


1 2 Next >>