UMLS:C0043167 - FACTA Search

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Query: UMLS:C0043167 (pertussis)
19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In homogenate of rat olfactory bulb, the opioid receptor agonists beta-endorphin, Leu-enkephalin, and dynorphin A stimulated adenylate cyclase activity in a concentration-dependent manner, with half-maximal effects displayed at 22, 63, and 176 nM, respectively. The maximal stimulation of the enzyme activity corresponded to about a 40% increase of basal activity for all three peptides. Naloxone antagonized the stimulation of beta-endorphin, Leu-enkephalin, and dynorphin A, with pA2 values of 8.0, 7.7, and 8.1, respectively. Kinetic analysis performed with Leu-enkephalin showed that the opioid peptide increased the Vmax of the enzyme, without changing the Km for the substrate Mg-ATP. Moreover, the opioid stimulation was associated with a significant increase of the affinity of the enzyme for Mg2+ activation and occurred in membranes incubated in a Ca2(+)-free medium. Addition of exogenous GTP at micromolar concentrations was absolutely necessary for the detection of the opioid effect. Treatment of olfactory bulbs with cholera toxin did not alter the stimulation of adenylate cyclase by Leu-enkephalin. However, the opioid stimulation disappeared in membranes obtained from bulbs injected with pertussis toxin. These results demonstrate the presence in the brain of a new functional class of opiate receptors coupled to stimulation of adenylate cyclase via a transduction mechanism that is Ca2+ independent and seems to involve a pertussis toxin-sensitive GTP-binding protein.
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PMID:Naturally occurring opioid receptor agonists stimulate adenylate cyclase activity in rat olfactory bulb. 167 23

Low (nanomolar) concentrations of opioid agonists prolong the calcium-dependent component of the action potential duration (APD) of many dorsal root ganglion (DRG) neurons, whereas higher (micromolar) levels shorten the APD. Both effects are blocked by naloxone (1-10 nM). Opioid-induced APD prolongation appears to be mediated by excitatory opioid receptors that are positively coupled via a cholera toxin-A-sensitive Gs protein to adenylate cyclase/cyclic AMP-dependent ion conductances, whereas opioid-induced APD shortening is mediated by inhibitory receptors linked via pertussis toxin-sensitive Gi/Go proteins. Cholera toxin-B subunit, which binds to GM1 ganglioside, also selectively blocks opioid-induced APD prolongation. After brief treatment with GM1 ganglioside, the opioid agonists, dynorphin (1-13) or morphine, prolong the APD at femtomolar vs. the usual nanomolar concentrations, whereas no significant alterations were observed in the sensitivity of these GM1-treated cells to opioid inhibitory effects elicited by higher opioid concentrations. The present study shows that the opioid antagonists, naloxone or diprenorphine (1-30 nM), did not alter the APD of naive DRG neurons. In contrast, after GM1 treatment (1 microM, greater than 10 min), both opioid antagonists (but not (+)naloxone) unexpectedly prolonged the APD of most of the GM1-treated cells, but still continued to antagonize opioid-induced APD shortening. These results suggest that the supersensitivity of GM1-treated DRG neurons to the excitatory effects of opioid agonists and antagonists is due primarily to a remarkably increased efficacy of excitatory Gs-coupled opioid receptor functions, similar to the opioid excitatory supersensitivity that we have recently observed in chronic opioid-treated DRG neurons.
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PMID:After GM1 ganglioside treatment of sensory neurons naloxone paradoxically prolongs the action potential but still antagonizes opioid inhibition. 173 Oct 37

The intracerebroventricular (i.c.v.) administration of pertussis toxin (0.5 microgram) to rats significantly reduced the hypothermic and behavioural effects (episodic bizarre postures characterized by limb rigidity and followed by barrel rolling) induced by i.c.v. dynorphin A (10 micrograms). These central effects of dynorphin A thus appear to be initiated at a receptor site that interacts with G proteins substrates sensitive to pertussis toxin. Dynorphin A-induced hypothermia was also significantly reduced by i.c.v. pretreatment with the Ca2+ antagonist, verapamil (10 micrograms), although verapamil per se did not modify the behavioural effects elicited by the peptide.
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PMID:Gi proteins and calcium in dynorphin-induced hypothermia and behaviour. 197 19

The kappa-selective opioid peptide dynorphin A (DYN) inhibits neuronal adenylate cyclase activity and reduces neuronal voltage-dependent calcium currents. It is not yet known, however, whether the regulation of calcium channel activity is dependent on or independent of the adenylate cyclase/cAMP system. We used the whole-cell variation of the patch clamp technique to show that DYN reversibly reduced, in a naloxone-sensitive manner, calcium currents in acutely dissociated rat nodose ganglion neurons. DYN slowed the rate of current activation and had a greater effect on currents evoked from relatively negative holding potentials. These actions were mimicked by guanosine 5'-[gamma-thio]triphosphate, which activates GTP-binding proteins (G proteins), and were blocked by pretreatment with pertussis toxin, which inactivates Gi- and Go-type G proteins. In contrast, calcium currents recorded in the presence of the catalytic subunit of the cAMP-dependent protein kinase (AK-C), included in the recording pipette, increased in magnitude throughout the recording. DYN was applied to neurons before and after the effect of AK-C became apparent; the reduction of calcium currents by DYN was greater in the presence of AK-C than in its absence. We conclude that the acute reduction of neuronal calcium currents by DYN occurred by means of activation of pertussis toxin-sensitive Gi- or Go-type G proteins. The persistence of the action of DYN in the presence of AK-C indicates, however, that this effect was independent of a reduction of the activity of the adenylate cyclase/cAMP system and suggests in addition that phosphorylated channels may be preferentially inhibited by DYN.
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PMID:Dynorphin A and cAMP-dependent protein kinase independently regulate neuronal calcium currents. 197 50

The effect of both chronic and acute lithium treatment on hypothalamic opioid peptides was investigated. Acute treatment with lithium was found to stimulate the release of beta-endorphin, dynorphin and Met-enkephalin from perfused rat hypothalamic slices. Application of tetrodotoxin was found to have no effect upon the stimulation indicating it to be mediated at the nerve terminal level. The release of hypothalamic opioid peptides is known to be under the chronic control of a system of inhibitory autoreceptors. Blockade of these autoreceptors with, for example, the opioid receptor antagonist naloxone causes a release of all three opioid peptides. Simultaneous addition of naloxone and lithium was found to have no additive effect on the release of any opioid, suggesting lithium acts via an inhibition of the inhibitory autoreceptor. Preincubation with pertussis toxin prevented the lithium stimulation of dynorphin and Met-enkephalin, but not beta-endorphin, release, indicating lithium interacts with a G-protein to affect the autoreceptor controlling the release of dynorphin and Met-enkephalin. Chronic treatment with lithium in vivo (10 days) had no effect on the basal release or hypothalamic content of any of the opioids, but prevented the naloxone-stimulated release of dynorphin and Met-enkephalin in vitro. Long-term treatment with lithium would thus appear to inactivate the autoreceptor(s) controlling their release. These data demonstrate a lithium-stimulated release of hypothalamic beta-endorphin, Met-enkephalin and dynorphin, apparently mediated via an inhibition of the autoreceptors controlling their release. Chronic treatment with lithium permanently inactivated the autoreceptor(s) controlling the release of dynorphin and Met-enkephalin but not beta-endorphin. Lithium would appear to mediate its effects upon Met-enkephalin and dynorphin release via an interaction with a pertussis toxin-sensitive G-protein. The mechanisms underlying its release of beta-endorphin are at present uncertain.
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PMID:Stimulation of hypothalamic opioid peptide release by lithium is mediated by opioid autoreceptors: evidence from a combined in vitro, ex vivo study. 217 62

The aim of the present study has been to characterize the regulation by opiates of 45Ca2+ influx in rat spinal cord-dorsal root ganglion cocultures. We have demonstrated that K+-induced depolarization, in the presence of the Ca2+ channel agonist Bay K8644, stimulated Ca2+ influx (3-4-fold) via the dihydropyridine class of voltage-dependent Ca2+ channels. While mu and delta opiates had no effect, kappa opiate agonists (e.g. U50488, dynorphin) profoundly depressed the stimulated Ca2+ influx (86% inhibition at 100 microM U50488). The kappa agonist action was stereospecific and could be reversed by the opiate antagonist naloxone. The inhibition produced by kappa agonists was greatly diminished following pertussis toxin treatment, and this effect was accompanied by toxin-induced ADP-ribosylation of a 40-41-kDa protein. This suggests that kappa opiate receptors are negatively coupled to voltage-dependent Ca2+ channels, via a pertussis toxin-sensitive GTP-binding protein. Basal 45Ca2+ uptake, stimulated by adenylate cyclase activators (forskolin and cholera toxin), was potently inhibited by kappa opiates suggesting that, under conditions of neurohormonal stimulation of adenylate cyclase, kappa receptors are coupled to Ca2+ channels indirectly via the adenylate cyclase complex. In addition, cAMP-independent coupling pathways may also be involved.
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PMID:Kappa opiate agonists inhibit Ca2+ influx in rat spinal cord-dorsal root ganglion cocultures. Involvement of a GTP-binding protein. 253 41

Somatostatin, morphine, and opioids inhibit transmitter release at intact neuromuscular junctions between ciliary ganglion neurons and the choroidal smooth muscle of the chick eye. Somatostatin and morphine, however, have no effect on release from terminals on the striated muscle target of the ciliary ganglion, the iris. In neuronal terminals of both the choroid and the iris, a high-affinity Na+-dependent choline uptake-mediated ACh synthesis is present at hatching. Both tissues exhibit a basal release of 3H-ACh which is potentiated severalfold during a 5 minute incubation in 55 mM K+ Tyrodes. Fifty percent of the basal release and 100% of the stimulated release are Ca2+ dependent and probably mediated through N-like voltage-dependent Ca2+ channels. Co-incubation of the choroid with 10 microM morphine sulfate blocks approximately 90% of the stimulated release. The same effect is seen with 100 nM somatostatin, 10 microM dynorphin, and 100 microM met-enkephalin arginine phenylalanine. Preincubation of the excised choroid with pertussis toxin (200 ng/ml) reverses the inhibitory effects of both morphine and somatostatin. In contrast, 3H-ACh release from terminals in the striated iris is not affected by either morphine or somatostatin at micromolar levels. These results suggest that both opiate and somatostatin receptors are present in the choroid target and that they may act through a final common pathway to modulate ACh release via G proteins. Second messengers such as cyclic AMP or diacylglycerol do not appear to mediate these effects; neither increasing cAMP levels in terminals nor activation of protein kinase C affects evoked release or its inhibition by morphine or other neuromodulators. It is unclear whether endogenous neuromodulation occurs in this system, although somatostatin-like immunoreactivity can be demonstrated in terminals of choroid neurons.
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PMID:Opiate and peptide inhibition of transmitter release in parasympathetic nerve terminals. 256 61

Acutely, morphine and D-ala2-D-leu-enkephalin (DADLE) inhibited adenylate cyclase in vitro in locus coeruleus (LC), dorsal raphe, frontal cortex and neostriatum and the inhibition by each agonist was blocked by the opiate-receptor antagonist naloxone. Although morphine was equally efficacious in the four brain regions examined (10-15% inhibition), DADLE inhibited cyclic AMP (cAMP) production to a greater extent in cortex and striatum (20-25% inhibition). Pertussis toxin treatment in vitro significantly reduced DADLE-inhibition of adenylate cyclase in all brain areas, indicating that this opiate response is mediated by a pertussis toxin-sensitive G-protein (i.e., Gi and/or Go). Chronic (in vivo) administration of morphine pellets for 5 days, treatment known to induce opiate tolerance and dependence, increased basal, GTP- and forskolin-stimulated adenylate cyclase in the LC, but not in the other three brain regions studied. DADLE was found to inhibit cAMP production in LC in vitro to the same extent in control and morphine-treated rats, suggesting a lack of opiate receptor tolerance. The morphine-induced increase in adenylate cyclase required chronic exposure to the opiate, as shorter treatment times, namely 2 hr and 1 day, failed to produce this effect. In fact, at 2 hr a small decrease in adenylate cyclase in the LC was observed that did not appear to be due to morphine being retained in the membrane fraction. Taken together, the findings of this study provide support for the view that changes in the cAMP system in the LC play a role in mediating acute opiate action as well as in underlying the development of opiate tolerance, dependence and/or withdrawal.
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PMID:Acute and chronic opiate-regulation of adenylate cyclase in brain: specific effects in locus coeruleus. 284 24

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

In freshly isolated spinal dorsal horn (DH) neurons (laminae I-IV) of the young rat, the effects of dynorphin A1-17, U-50,488H and U-69,593 on inward currents induced by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate (KA) were studied under whole-cell voltage-clamp conditions. When the cells were clamped to a holding potential of -60 mV, co-application of dynorphin A1-17 (10(-6) M) and AMPA (2 x 10(-5) M) reversibly decreased the peak amplitude of the initial transient component of the AMPA-induced current in 72% of the examined cells. In addition, dynorphin (10 microM) in perforated patch-recordings consistently produced a decrease in the steady-state component of the AMPA response. The depressant effect was concentration-dependent (IC50 = 86 nM) and reversible. The dynorphin A1-17-induced depression of the AMPA response was associated with slowing of the response kinetics, including both a 10-90% rise-time and time constant of decay. The AMPA-induced currents were modulated by dynorphin not only during the co-administration but also after the removal of the peptide. Dynorphin increased the initial peak AMPA current in 42% of the examined cells. Similar as with dynorphin A1-17, the peak amplitude of the AMPA-induced current was reversibly suppressed in the presence of 1 microM U-50,488H and U-69,593 in 75% and 86% of the examined cells, respectively. Naloxone and the kappa 1-selective antagonist norbinaltorphimine (nor-BNI) blocked the initial depressant but not late excitatory effects of dynorphin A1-17 and U-50,488H. This antagonistic effect of naloxone and norbinaltorphimine suggests that the depressant effect of dynorphin A1-17 on the AMPA-activated conductance is a true opioid, probably kappa 1-opioid receptor-mediated event. In contrast, the dynorphin-induced late potentiation of AMPA/KA responses appears to be a non-opioid effect since it was not inhibited by nor-BNI, CTAP and naltrindole, the selective kappa-, mu- and delta-opioid receptor blocking agents, respectively. Pretreatment of DH neurons with pertussis toxin blocked the depressant action of dynorphin A1-17, indicating that a Gi- or Go-type G protein was required for this effect on AMPA-activated currents. Intracellular dialysis with a highly specific peptide inhibitor (peptide 6-22) of the cAMP-activated protein kinase (PKA), and with Rp-cAMPS, prevented the depressant effect of dynorphin A1-17. In addition, staurosporine, a nonselective kinase inhibitor, blocked the dynorphin depression of the AMPA response.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The opioid peptide dynorphin modulates AMPA and kainate responses in acutely isolated neurons from the dorsal horn. 753 29

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