Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The respiratory responses to systemic infusion of the opioid peptide, [D-Ala2, D-Leu5]enkephalin (ENK) were determined in 39 unanesthetized tracheotomized rabbits (age range 1-20 days). At all ages, ventilation (VE), measured in a body plethysmograph, was depressed after ENK infusion in association with a decrease in CO2 elimination (VCO2) and body temperature. The degree of VE depression varied inversely with increasing age and was directly related to changes in mean inspiratory flow (i.e., VT/TI) while the ratio of inspiratory to total breath duration (TI/TT) was unaltered, except in rabbits under about 1 wk of age. Maturational differences in the VE response to ENK were related to age-dependent variation in the stability of the central inspiratory activity, which was manifested as periodic breathing with apnea in rabbits under about 5 days of age. Since the initial inspiratory volume-time profile was little affected by ENK and vagal afferent influence on respiration was not diminished, the depression in VE could be explained by an inhibition of the central inspiratory "off-switch" threshold and delay in central inspiratory "on-switching." All effects of ENK were reversed by the opiate antagonist, naloxone.
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PMID:Maturational effect of enkephalin on respiratory control in newborn rabbits. 717

1 Methionine (Met)-enkephalin, leucine (Leu)-enkephalin and their synthetic analogues were tested for effects on the spontaneous release of cortical acetylcholine (ACh) in vivo. The ability of naloxone to reverse the action of enkephalins on ACh release was compared with its action against morphine. An enkephalin analogue, structurally related to Met-enkephalin, was tested for opiate antagonistic activity in ACh release experiments. 2 Intraventricular administration of Met-enkephalin, Leu-enkephalin, D-Ala2-Met5-enkephalinamide (DALA) and D-Ala2-D-Leu5-enkephalin (DALEU) produced a dose-related inhibition of cortical ACh release. Met- and Leu-enkephalin were very similar both in their potency and the time course of their action on ACh release. Both DALA and DALEU were more potent and had a longer duration of action than Leu-enkephalin. Systemic injections of two pentapeptides, D-Met2-Pro5-enkephalinamide and D-Ala2-MePhe4-Met5(O)-ol-enkephalin (33,824), produced a sustained inhibition of cortical ACh release. 3 Naloxone, administered systemically following the depression of ACh release induced by either intraventricular injections of enkephalins (DALA or DALEU), or systemic injections of enkephalins (D-Met2-Pro5-enkephalinamide or 33,824), reversed this depression and restored the release to baseline levels. The effect of D-Met2-Pro5-enkephalinamide on the release of ACh was reversed by naloxone with difficulty. Naloxone also reversed the inhibitory effect of systemic morphine and this reversal was associated with a large overshoot of ACh release. The latter was never observed in the enkephalin experiments. 4 Intraventricular injection of the pentapeptide, D-Ala2-D-Ala3-Met5-enkephalinamide (TAAPM), at doses that did not influence the basal ACh release, blocked or reversed the inhibitory effect of morphine on this release. This peptide did not block the effect of the non-opiate, chlorpromazine, under similar conditions. In two experiments TAAPM failed to reverse the inhibition of ACh release produced by systemically injected enkephalin, D-Met2-Pro5-enkephalinamide. 5 Effects of morphine and enkephalin on ACh release are discussed in terms of their action on difference opiate receptors.
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PMID:Action of enkephalin analogues and morphine on brain acetylcholine release: differential reversal by naloxone and an opiate pentapeptide. 747 Jul 36

1. Single pulse electrical field stimulation (EFS, 0.5 ms pulse width, 60 V at a frequency of 0.05 Hz) induced twitch contractions of mucosa-free circular muscle strips from the guinea-pig proximal colon which were abolished by atropine (0.3 microM), tetrodotoxin (0.3 microM) or omega-conotoxin GVIA (0.1 microM). 2. Various opioid receptor agonist concentration-dependently inhibited twitches with the following rank order of potency (EC50 values in brackets): U 50488 (0.31 nM) > dermorphin (4.3 nM) = dynorphin A (1-13) (6.2 nM) > [D-Ala2, N-MePhe4, Gly5-ol]-enkephalin (DAMGO, 33.5 nM) = [D-Ala2, D-Leu5]-enkephalin (DADLE, 60 nM) > [D-Pen2, D-Pen2, D-Pen5]-enkepahlin (DPDPE, 1144 nM). 3. Peptidase inhibitors (captopril, thiorphan and bestatin, 1 microM each) did not modify the amplitude of twitches. In the presence of peptidase inhibitors the concentration-response curve to dynorphin A (1-13) was displaced to the left to yield an EC50 of 0.35 nM, comparable to that of the selective kappa receptor agonist, U50488. The curves to the other opioid receptor agonist were unaffected by peptidase inhibitors. 4. DPDPE, DADLE, dermorphin and DAMGO consistently induced a concentration-unrelated transient increase in basal tone and a small and transient facilitation of twitches before development of their inhibitory effect. These transient excitatory effects were not observed upon application of dynorphin A (1-13) or U 50488. The contraction produced by DPDPE (30 nM) was largely inhibited (> 80%) by 1 microM atropine. 5. Twitches suppression induced by dynorphin A (1-13) (30 nM) was partly reversed (46 +/- 8%, n = 6) by naloxone (0.3 microM). The potent and selective kappa opioid receptor antagonist nor-binaltorphimine (Nor-BNI, 3-100 nM)) did not affect the amplitude of twitches and potently antagonized (pKB 9.83 +/- 0.09, n = 10) the inhibitory effect of dynorphin. 6. Naloxone (1-300 nM) concentration-dependently depressed the cholinergic twitches: this depressant effect was largely counteracted in the presence of apamin (0.1 microM) and NG-nitro-L-arginine (30 microM) which potentiated cholinergic twitches on their own. 7. Dynorphin A (1-13) (10 nM, n = 6) did not affect the contractile response to exogenous acetylcholine (1 microM), indicating that depression of evoked twitches occurs prejunctionally. 8. We conclude that multiple opioid receptors modulate cholinergic twitches in the circular muscle of guinea-pig proximal colon. While mu and delta opioid receptor agonists produced mixed excitatory and inhibitory effects, kappa opioid receptors, activated by sub-nanomolar concentrations of dynorphin A (1-13), mediate a powerful and pure prejunctional inhibition of acetylcholine release.
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PMID:Role of kappa opioid receptors in modulating cholinergic twitches in the circular muscle of guinea-pig colon. 892 49

1. Membrane potential (Vm) and resistance (Rm) of ventral respiratory group (VRG) neurons were measured in the isolated brainstem-spinal cord from newborn rats during bath application of the opioid receptor agonists fentanyl or [D-Ala2, D-Leu5]-enkephalin (Ala-Leu-Enk) and of the prostaglandin E1 (PGE1). 2. PGE1 (0.1-3 microM) and fentanyl or Ala-Leu-Enk (1-50 microM) produced depression and, at higher doses, block of inspiratory nerve activity and respiration-related postsynaptic potentials. This apnoea was associated with hyperpolarization and Rm fall in 25% of thirty-two VRG neurons tested, whereas resting Vm and Rm were not changed in the other cells. 3. The selective mu- and delta-receptor blockers naloxonazine (10-20 microM) and naltrindole (50-100 microM) antagonized the effects of 5 microM fentanyl and 50 microM Ala-Leu-Enk, respectively. 4. Opioid- and PGE1-evoked respiratory depression was reversed upon elevation of endogenous cAMP levels by stimulating adenylyl cyclase with 100 microM forskolin, activating dopamine D1 receptors with 50-100 microM 6-chloro-7,8-dihydroxy-3-allyl-1-phenyl-2, 3,4,5-tetrahydro-1H-3-benzazepine (6-chloro-APB) or preventing cAMP breakdown with 50-100 microM isobutylmethylxanthine. 5. The results indicate that opioid- or prostaglandin-induced respiratory depression is due to a fall in cAMP levels in cells responsible for generation of rhythm or providing a tonic drive to the respiratory network. 6. We suggest that elevation of cAMP levels is an effective antidote in neonates against such forms of respiratory depression.
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PMID:cAMP-dependent reversal of opioid- and prostaglandin-mediated depression of the isolated respiratory network in newborn rats. 935 Jun 24

Previous studies show that infusion of hibernating woodchuck albumin (HWA) induces hibernation in summer-active ground squirrels and results in profound behavioral and physiological depression in primates. These effects are reversed by the administration of opiate antagonists, suggesting that the putative hibernation induction trigger (HIT) may act through opioid receptors. We have demonstrated that both HIT-containing plasma and the synthetic alpha opioid D-Ala2-D-Leu5-enkephalin (DADLE), which mimics the activity of HIT in hibernators, extend tissue survival time of a multi-organ autoperfusion system by 3-fold. In this study we present the first data showing biological activity with a much more highly purified plasma fraction from hibernating woodchucks, identified as the hibernation-related factor (HRF). Both the HRF and DADLE show opiate-like contractile inhibition in the mouse vas deferens (Mvd) bioassay. We also have preliminary evidence in an isolated rabbit heart preparation indicating that the HRF and DADLE act similarly to restore left ventricular function following global myocardial ischemia. Furthermore, we have partially sequenced an alpha 1-glycoprotein-like 88 kDa hibernation-related protein (p88 HRP) present in this fraction, which may prove to be the blood-borne HIT molecule.
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PMID:Isolation and partial characterization of an opioid-like 88 kDa hibernation-related protein. 978 70


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