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)

Neuropeptide Y (30-1000 nmol/l) significantly inhibited the fractional stimulation-induced outflow of radioactivity from mouse atria preincubated with [3H]-noradrenaline. The inhibitory effect of neuropeptide Y was observed at all frequencies tested (2, 5 and 10 Hz) as well as after alpha-adrenoceptor blockade with phentolamine (1 mumol/l). A combination of 8-bromo adenosine cyclic-3'-5'-monophosphate (90 or 270 mumol/l) with the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (100 mumol/l) was used to saturate maximally the adenylate cyclase system and these drug combinations significantly enhanced the stimulation-induced outflow of radioactivity. However, neuropeptide Y inhibited the stimulation-induced outflow in the presence of these drugs, suggesting that the inhibitory effect of neuropeptide Y was not due to decreasing endogenous cyclic AMP formation. Finally, atria from mice treated with pertussis toxin were used. In this case, the inhibitory effect of neuropeptide Y on the stimulation-induced outflow of radioactivity was still observed suggesting that inhibitory prejunctional neuropeptide Y receptors are not coupled to a pertussis toxin-susceptible G protein.
 ...
PMID:Inhibition of noradrenaline release by neuropeptide Y in mouse atria does not involve inhibition of adenylate cyclase or a pertussis toxin-susceptible G protein. 248 50

The role of G-proteins in the mediation of the cardiovascular effects of neuropeptide Y and the alpha 2-adrenoceptor agonist clonidine was investigated by injections of pertussis toxin (10 micrograms/30 microliters, i.v.t., 24 h) in the awake unrestrained male rat. Treatment with pertussis toxin was found to inhibit the hypotensive and bradycardic actions of neuropeptide Y (1250 pmol) and the hypotensive actions of clonidine (1875 pmol). Control experiments showed that treatment with pertussis toxin caused an approximately 50% reduction in the back-ADP-ribosylation of GTP-binding proteins. These results suggest that G-proteins mediate the central cardiovascular actions of neuropeptide Y and clonidine.
 ...
PMID:Pertussis toxin treatment counteracts the cardiovascular effects of neuropeptide Y and clonidine in the awake unrestrained rat. 250

We have previously demonstrated that neuropeptide Y (NPY) inhibits voltage sensitive Ca2+ channels in rat dorsal root ganglion neurons and that this effect is mediated by a pertussis toxin-sensitive, guanyl nucleotide-binding protein (G-protein). We now demonstrate that NPY can also stimulate the synthesis of inositol trisphosphate (InsP3) and diacylglycerol in dorsal root ganglion neurons. The effects of NPY were compared with those of bradykinin (BK) which also stimulates phosphoinositide turnover in these cells. NPY-stimulated InsP3 synthesis could be completely blocked by treatment with pertussis toxin and significantly enhanced by cholera toxin although not by other agents which raised cellular concentrations of cyclic AMP. In contrast, the effects of BK were completely unaltered by either toxin. Furthermore the maximal effects of BK and NPY were additive. In spite of the lack of toxin effects, stimulation of InsP3 synthesis produced by BK was clearly mediated by a G-protein. Thus BK stimulated InsP3 production in digitonin-permeabilized neurons, and these effects were enhanced by guanosine 5'-O-(3-thiotriphosphate) and blocked by guanosine 5'-O-(2-thiodiphosphate). The stimulatory effects of both NPY and BK were also blocked by treatment of neurons with phorbol esters. Fura-2-based microfluorimetry of single dorsal root ganglion neurons demonstrated that both BK and NPY increased cytoplasmic-free Ca2+ concentration and that both peptides could produce this effect in the same neuron. Both agents could still increase cytoplasmic-free Ca2+ concentration in Ca2+-free medium indicating that the source of the Ca2+ was an intracellular store. Thus, both NPY and BK can activate InsP3 synthesis in the same cell but seem to utilize different G-proteins. NPY utilizes a pertussis toxin-sensitive G-protein and BK a toxin-insensitive one.
 ...
PMID:Two different G-proteins mediate neuropeptide Y and bradykinin-stimulated phospholipid breakdown in cultured rat sensory neurons. 254 Jan 85

The intracellular messengers that seem to be involved in renin secretion (RS) from juxtaglomerular cells (JG) are calcium (Ca), cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). Unlike the majority of secretory systems, an increase in intracellular Ca concentration and calmodulin and protein kinase C activation inhibit RS. The intracellular Ca concentration in JG cells can be modified if: 1) the normal mechanisms of Ca extrusion of these cells is altered; 2) the calcium output is blocked by lanthanum; 3) the function of the voltage-sensitive Ca-channels is modified; 4) uptake or liberation of Ca from endoplasmic reticulum is modified; 5) plasmatic membrane is bypassed with calcium ionophores such as A 23187. 6) JG cells are stimulated by hormones that increase Ca and activate protein kinase C such as angiotensin II, vasopressin or alpha-1 adrenergic agonists; 7) extracellular Ca concentration increases or decreases. RS is stimulated by dibutyryl cAMP, cAMP phosphodiesterase inhibitors and by hormones and agents that activate adenylate cyclase (beta adrenergic agonists, bradykinin, histamine, forskolin and ethylcarboxamide adenosine). On the contrary, RS is inhibited by hormones and agents that inhibit adenylate cyclase such as: alpha-2 adrenergic agonists, neuropeptide Y, angiotensin II and cyclohexyladenosine. Pertussis toxin increases basal RS, blocks the inhibition by agents and hormones which inhibit adenylate cyclase and potentiate the stimulation produced by beta-adrenergic agonists. In JG cells, atrial natriuretic peptide inhibits RS, increases cGMP and decreases cAMP. The increase in cGMP correlates well with the inhibition of RS.
 ...
PMID:[Intracellular messengers in the regulation of renin secretion]. 255 Oct 26

The effect of neuropeptide Y (NPY) on cell contractions of ventricular myocytes isolated from the adult rat heart was investigated. Maximum changes in cell length (dL) during stimulated (0.5 Hz) contractions were determined in presence of the phosphodiesterase inhibitor Ro 20-1724 (0.5 mM) and adenosine deaminase (5 U/ml). Under these basal conditions NPY (10(-6) M) reduced dL by 39% of control. Isoproterenol (10(-6) M) increased dL by 105% of control; the EC50 was 2 x 10(-9) M. NPY reduced the increase in dL achieved by isoproterenol in a dose dependent manner. The IC50 value was 1 x 10(-9) M and NPY (10(-6) M) produced complete inhibition. In the absence of the phosphodiesterase inhibitor the IC50 was 4 x 10(-9) M. The EC50 of isoproterenol and IC50 of NPY producing accumulation of cAMP in myocytes (Millar et al. 1988) exceeded the respective values of dL by one order of magnitude. Prior treatment of the myocytes with pertussis toxin abolished the potency of NPY to antagonize the increase in dL by isoproterenol while not interfering with the response to the beta-agonist. These results demonstrate a negative inotropic effect of NPY on the ventricular myocardial cell. Complete abolition of the effect of NPY by pertussis toxin indicate that this effect is mediated by a sarcolemmal receptor for NPY linked to adenylate cyclase via an inhibitory guanine nucleotide binding protein.
 ...
PMID:The negative inotropic effect of neuropeptide Y on the ventricular cardiomyocyte. 255 54

The effect of intracerebroventricular injections of pertussis toxin were investigated on the neuropeptide Y-induced modulation of alpha 2-adrenoceptor binding in membranes from the dorsomedial medulla oblongata of the rat. Concentration-response experiments showed that neuropeptide Y reduced the binding affinity of the alpha 2-agonist, p-[3H]aminoclonidine, with a maximal effect of 30% at 3-30 nM. Pertussis toxin treatment (10 micrograms, 24 h) counteracted this modulation, without reducing the binding of neuropeptide Y to its own receptor. The results indicate that pertussis toxin-sensitive G-proteins are essential for the mediation of the intramembrane interaction between neuropeptide Y receptors and alpha 2-adrenoceptors.
 ...
PMID:Pertussis toxin treatment counteracts intramembrane interactions between neuropeptide Y receptors and alpha 2-adrenoceptors. 255 98

The peptides neuropeptide Y (NPY) and bradykinin (BK) both inhibited Ca2+ currents in rat dorsal root ganglion neurons (DRG) in vitro. The effects of both peptides were completely blocked by treatment of cells with pertussis toxin. Based on antigenic determinants, DRG cells contained at least two pertussis toxin substrates, alpha o (Mr, 39 kd) and alpha i2 (Mr, 40 kd). We examined the ability of three purified bovine alpha subunits (identified with antibodies as alpha o, alpha i1, and alpha i2) to reconstitute the inhibitory effects of NPY and BK. Reconstitution of NPY effects occurred according to the potency series alpha o greater than alpha i1 much greater than alpha i2. However, in the case of BK all three G proteins were approximately equally effective. Whereas complete reconstitution of NPY effects could be obtained with alpha o, no single alpha subunit produced complete reconstitution of BK. Combinations of alpha o and alpha i2, however, were able to completely reconstitute the effects of BK. Thus several G proteins can effect the regulation of Ca2+ channels in these cells. However, neurotransmitters may be selective in the G proteins or combinations of G proteins utilized to achieve this regulation.
 ...
PMID:Differential G protein-mediated coupling of neurotransmitter receptors to Ca2+ channels in rat dorsal root ganglion neurons in vitro. 256 Mar 87

The effect of neuropeptide Y (NPY) on adenylate cyclase activity was examined in ventricular myocytes isolated from the adult rat heart. In the presence of the phosphodiesterase inhibitor Ro 20-1724 (0.5 mM) and adenosine deaminase (5 U/ml), these intact cells accumulate cyclic AMP when stimulated by isoproterenol. NPY (10(-9) to 10(-6) M) reduced the degree of cAMP accumulation achieved by 10(-7) M isoproterenol in a dose dependend manner by 10 to maximally 48%. The IC50 value was 3 x 10(-8) M NPY. A maximal concentration (10(-6) M) of N6-phenylisopropyladenosine (PIA) decreased cAMP levels by 39%, i.e. to a similar extent. Prior treatment of the myocytes with pertussis toxin (1 microgram/ml for 6 h) increased the mean stimulated values in the presence of isoproterenol (10(-7) M) by a factor 4.1. In such cells, NPY and PIA were ineffective in antagonizing the stimulation of cAMP production by isoproterenol. These results indicate that the ventricular myocyte has receptors for NPY, similar to the A1 adenosine-receptor in that they are linked to the adenylate cyclase by an inhibitory guanylate binding protein.
 ...
PMID:The antiadrenergic effect of neuropeptide Y on the ventricular cardiomyocyte. 285 10

Previous studies have demonstrated a similarity between the ability of neuropeptide Y (NPY) and clonidine to inhibit renin release and inhibit cAMP production. We therefore compared the effects of clonidine and NPY on the excretion of sodium and water in anesthetized rats which were unilaterally nephrectomized (right kidney) 10 days prior to the experiment. On the experimental day, rats were anesthetized (nembutal) and the left kidney exposed for the intrarenal infusion of the study drugs. The lowest dose of NPY (0.3 microgram/kg per min) investigated failed to alter renal function. Clonidine (0.3 microgram/kg per min) and NPY (1 microgram/kg per min) produced a similar increase in urine volume. Only NPY increased sodium excretion and osmolar clearance. Free water clearance was only increased by clonidine. Blood pressure and creatinine clearance were similar in all groups investigated. These effects were attenuated by pretreatment with pertussis toxin (5 days). The ability of pertussis toxin to block these effects suggests that the renal effects of NPY and clonidine are coupled to a G protein, conceivably the inhibitory Gi protein of the adenylate cyclase system. The disparate effects on sodium excretion and on free water and osmolar clearance indicate that the effects of these compounds may be mediated through the inhibition of different pools of hormonally stimulated cAMP.
 ...
PMID:Disparate effects of neuropeptide Y and clonidine on the excretion of sodium and water in the rat. 290 68

Using 125I-labeled neuropeptide Y (NPY) and peptide YY (PYY), we demonstrated the existence of specific receptors for these peptides on rat dorsal root ganglion (DRG) cells grown in primary culture. Scatchard analysis of membrane homogenates indicated that the peptides bound to 2 populations of sites, with approximate affinities of 0.08 and 6.5 nM. Only low levels of binding were detected on sympathetic neurons cultured from the same animals or on a variety of neuronal clonal cell lines. The binding of 125I-NPY and 125I-PYY to DRG cell membranes was considerably reduced by the nonhydrolyzable analog of GTP, Gpp(NH)p. The major effect of Gpp(NH)p was to reduce the number of lower-affinity NPY binding sites without altering the number of high-affinity binding sites. NPY potently inhibited Ca2+ currents recorded under voltage clamp in rat DRG cells. Both the transient and sustained portions of the Ca2+ current were inhibited. The inhibitory effects of NPY were completely blocked following treatment of the cells with pertussis toxin. Depolarization elicited a large influx of Ca2+ into DRG neurons as assessed using fura-2-based microspectrofluorimetry. This influx of Ca2+ could be partially inhibited by NPY. Furthermore, NPY effectively inhibited the depolarization-induced release of substance P from DRG cells in vitro. Thus, NPY may be an important regulator of sensory neuron function in vivo.
 ...
PMID:Neuropeptide Y modulates neurotransmitter release and Ca2+ currents in rat sensory neurons. 290 13


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>