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Biomedical subjects

A Dray

Publications and source records attributed to A Dray.

At least 109 records · Page 6Linked to original sources
PubMed1985

Proenkephalin A fragments exhibit spinal and supraspinal opioid activity in vivo.

The inhibition of reflex urinary bladder contractions, recorded isometrically in the urethane-anesthesized rat, was used as an index of central opioid activity. Inhibition of bladder activity has been shown to be mediated both spinally and supraspinally by mu and delta opioid receptors. Using this model a number of neuropeptide fragments of the proenkephalin A molecule (peptide F, peptide E, BAM 22P, BAM 12P, Met5-enkephalin-Arg6,Phe7,Leu8, Met5-enkephalin-Arg6,Phe7, Met-enkephalin, Leu-enkephalin) were tested for in vivo activity. Each of the fragments inhibited reflex bladder contractions when administered by bolus microinjection into a lateral ventricle (i.c.v.) or intrathecally into the spinal subarachnoid space (between L3 and L4 vertebra). The larger molecular weight peptides produced more prolonged inhibition of bladder activity than the smaller molecular weight ones, with the rank order of activity being similar at spinal and supraspinal sites: peptide F greater than or equal to peptide E = BAM 22P greater than BAM 12P greater than Met5-enkephalin-Arg6,Phe7,Leu8 = Met5-enkephalin-Arg6,Phe7 greater than or equal to Met-enkephalin = Leu-enkephalin. The relative receptor selectivity of each fragment was further determined using the opioid antagonists naloxone (mu receptors) and ICI 174,864 (N, N-diallyl-Tyr-Aib-Aib-Phe-Leu-OH: Aib = alpha-aminoisobutyric acid) (delta receptors). The activity (Ke) of each antagonist against equieffective doses of the highly selective opioid receptor ligands [D-Ala2,Me-Phe4,Gly(ol)5]enkephalin (mu receptors) and [D-Pen2,D-Pen5]enkephalin (delta receptors) was compared with that against the proenkephalin A fragments.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Evidence that naloxonazine produces prolonged antagonism of central delta opioid receptor activity in vivo.

Intracerebroventricular (i.c.v.) administrations of the postulated mu 1 opioid receptor antagonist naloxonazine produced an increase in the frequency of urinary bladder contractions recorded isometrically in the anesthetized rat. This substance also antagonized the inhibition of spontaneous bladder contractions produced by submaximal i.c.v. doses of the highly selective mu opioid agonist [D-Ala2-MePhe4,Gly-(ol)5]enkephalin (DAGO) and the delta opioid agonist [D-Pen2,D-Pen5]enkephalin (DPDPE). The antagonism of DAGO was reversible but that of DPDPE lasted up to 30 h. These data suggest that endogenous opioids are involved in the central control of bladder motility and that naloxonazine is a long-lasting delta opioid receptor antagonist.

Animals↗
PubMed1984

Opioid receptor subtypes involved in the central inhibition of urinary bladder motility.

Intracerebroventricular morphine consistently inhibited spontaneous urinary bladder contractions recorded from the anesthetized rat. This effect was reversed by naloxone and appeared to be exerted within the forebrain. Neither dynorphin-(1-13) nor U-50, 488 (kappa-agonists) affected bladder motility. Ethylketocyclazocine inhibited contractions only at higher doses, possibly due to mu-receptor interactions. Bladder activity was consistently inhibited by the mu-agonists morphiceptin and [D-Ala2, MePhe4, Gly-(ol)5]enkephalin (DAGO) and by [D-Ala2, D-Leu5]enkephalin (DADLE, delta-agonist). DAGO was the most potent compound tested. These observations support the involvement of mu- and possibly delta-receptors in the centrally mediated inhibition of urinary bladder motility by opioids.

Animals↗
PubMed1984

Motilin acts within the CNS to inhibit urinary bladder contractions.

Although peripheral actions have been shown for the brain-gut peptide, motilin, its localization in the CNS of mammals suggests some physiological role at this site. In the present experiments intracerebroventricular or intrathecal, but not peripheral, administrations of motilin produced a dose-related and naloxone reversible inhibition of the micturition reflex. Cross-tolerance was demonstrated between motilin and morphine in this respect. These data suggest a physiological role for motilin within CNS to alter urinary bladder motility, possibly through an enkephalinergic or naloxone-sensitive link.

Animals↗
PubMed1984

Spinal opioid receptors and inhibition of urinary bladder motility in vivo.

The effects of intrathecal injections of morphine and other opioid receptor selective drugs were tested on urinary bladder contractions in the anesthetized rat. Morphine produced dose-related inhibition of bladder motility which was abolished by naloxone. This action was also observed with mu- and delta-opioid receptor agonists but not with a kappa-opioid receptor agonist. These observations appear related to the urinary retention seen clinically with epidural administrations of morphine and support the hypothesis that urinary bladder activity is influenced by spinal opioid mechanisms involving mu- and delta-opioid receptors.

Animals↗
PubMed1984

Morphine and the centrally-mediated inhibition of urinary bladder motility in the rat.

Systemic administration of morphine consistently inhibited spontaneous urinary bladder contractions in the ketamine-anesthetized rat. In addition, i.c.v. morphine and levorphanol but not dextrophan inhibited bladder function by a naloxone-sensitive mechanism. Naloxone alone increased the frequency of bladder contractions and intravesicular pressure. Systemic loperamide did not affect bladder function while N,N- diallylnormorphinium only reversed bladder inhibition by morphine when administered i.c.v. These observations suggest that morphine inhibits bladder activity by a central mechanism and that endogenous opioids are involved in the central control of bladder function.

Animals↗
PubMed1984

Inhibition of urinary bladder contractions by a spinal action of morphine and other opioids.

Systemic morphine (1.0 mg/kg i.v. or s.c.) consistently inhibited spontaneous urinary bladder contractions recorded isometrically in the anesthetized rat. This effect was reversed by intrathecal (i.t.) naloxone (1-4 micrograms) at doses which were ineffective systemically. Intrathecal morphine was also inhibited bladder activity when administered into cervical, thoracic or lumbar regions but was faster acting and more effective when injected i.t. directly in the vicinity of the lumbo-sacral cord. The effect of morphine was dose-related and appeared to be a stereospecific opiate effect being observed with i.t. levorphanol but not with dextrorphan. Bladder inhibition by i.t. morphine at low doses could be overcome by increasing the intravesicular pressure. Intrathecal morphine was also reversed by i.t. (1-2 micrograms) or s.c. (0.5 mg/kg) naloxone but not by i.c.v. naloxone (1-2 micrograms). Intrathecal naloxone in naive animals increased bladder contraction frequency and intravesicular pressure only at high doses (10-20 micrograms i.t.). Bladder activity was consistently inhibited by [D-Ala2,MePhe4,Gly-(ol)5] enkephalin (mu agonist) and [D-Ala2-D-Leu5]enkephalin (delta agonist) but was unaffected by U-50, 488H i.t., (kappa agonist). The observations support the hypothesis that spinal opioid mechanisms are involved in the neurogenic control of bladder function and that systemically or i.t. administered opioid drugs mediate inhibition of bladder motility by spinal mechanisms involving mu and delta opioid receptors.

Animals↗
PubMed1983

A comparison of the release of substance P and some synthetic analogues from micropipettes by microiontophoresis or pressure.

The release of substance P (SP) and two analogues by iontophoresis or pressure from microelectrodes was compared. Substance P was released linearly by iontophoresis from electrodes while no release of the analogues was detected. [N-methylphenylalanine8, N-methylglycine9-] SP5-11 (DiMeC7) and [methyl-2-aminoethyl]11 SP (SP-DAE) were released from electrodes by pressure ejection with linear relationships in all cases between pressure and the amounts released. Under the tested experimental conditions, release of substance P by iontophoresis was between 2 and 3 orders of magnitude less than that by pressure over a given time. The release of substance P and the uncharged analogue DiMeC7 by pressure was very similar while release of SP-DAE was one order of magnitude less.

Electrophoresis↗
PubMed1982

Differential sensitivity of presumed dopaminergic and non-dopaminergic neurones in rat substantia nigra to electrophoretically applied substance P.

Substance P (SP) was administered by microelectrophoresis to physiologically identified substantia nigra neurones in halothane anaesthetized rats. Dopaminergic neurones of the substantia nigra compacta (SNC) were markedly less sensitive to SP than non-dopaminergic cells of the substantia nigra reticulata (SNR) when the peptide was administered with the same micropipettes. Identified substantia nigra neurones were also differentially sensitive to other putative transmitters including dopamine, 5-HT and acetylcholine. No interactions could be demonstrated between SP and the responses to other transmitters.

Acetylcholine↗
PubMed1981

Serotonin in the basal ganglia: functions and interactions with other neuronal pathways.

The serotoninergic innervation of the striatum and substantia nigra has been confirmed by a number of techniques. Inputs to both these regions appear to be inhibitory, but the possibility of non-serotoninergic pathways also originating from the raphe should be explored. No conclusions can yet be reached regarding the serotoninergic innervation of the globus pallidus or subthalamic nucleus. Behavioral studies show that serotonin, like dopamine, produces asymmetries when administered into the striatum or substantia nigra. These might be mediated though altered dopaminergic, cholinergic or GABA neuronal activity. Manipulation of the DRN or MRN serotoninergic projections suggest these nuclei serve different functional roles, though their exact nature is not understood. Defective serotonin neurotransmission is implicated in a number of neurological disorders, though a rational regimen of replacement therapy has been difficult to establish. Possibly, closer monitoring of relative transmitter deficiencies might select patients who would benefit from serotonin replacement therapy. Different types of serotonin receptors in basal ganglia suggest that altered serotonin neurotransmission might be involved in the catalepsy or dyskinesias produced by neuroleptic therapy.

Animals↗
PubMed1980

The effects of LSD and some analogues on the responses of single cortical neurons of the cat to optical stimulation.

The effects of lysergic acid diethylamide (LSD) and its analogues, 2-bromo-LSD (BOL) and methysergide, have been investigated on the responses to photic stimulation of single neurons in the striate cortex of the paralyzed, anesthetized cat. Systemic LSD (0.1--50 micrograms/kg, i.v.) produced: (a) enhancement or depression of evoked activity, the former being common with low, the latter with high doses; (b) changes in directional selectivity; and (c) changes in unstimulated background discharges. The effectiveness of the drug was reduced by repeated administration. Both BOL (10--75 micrograms/kg) and methysergide (100-700 micrograms/kg) produced effects qualitatively similar to LSD, but were considerably less potent. Microelectrophoretic administrations of LSD to single cortical neurons had actions similar to those caused by intravenous administration. BOL and methysergide required much larger currents to produce any effect and sometimes no effect could be induced by iontophoresis. It was concluded that these drugs influence visually evoked neuronal responses mainly by acting directly on cortical cells or synapses; and that the interference with visual cortical function could account for the distortion of visual perception caused by lysergic acid analogues; but that the hallucinogenic and psychotomimetic actions of LSD probably require additional subcortical effects.

Animals↗