Effects of some narcotics and antagonists on synaptosomal 3H-norepinephrine uptake

Ciofalo, Frank R.

doi:10.1016/0024-3205(72)90192-0

Cited by 23 publications

(6 citation statements)

References 5 publications

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“…The inactivity of morphine on [ 3 H]NA uptake in this study is in agreement with the work of Slotkin, Seidler and Whitmore, who were unable to show an effect of morphine 10~4 mol litre" 1 on [ 3 H]NA uptake in rat brain synaptosomes [3], although it did have a small (20 %) inhibitory effect on [ 3 H]5-hydroxytryptamine uptake. However, several studies using synaptosomes have shown an inhibitory effect of morphine on [ 3 H]NA uptake, but only in large concentrations (10~4 mol litre" 1 ) [2,12]. Furthermore, Montel and Starke demonstrated that several opioids, including morphine 10~5 mol litre" 1 , inhibited neuronal uptake of [ 3 H]NA in a perfused, isolated rabbit heart [13].…”

Section: Discussionmentioning

confidence: 99%

“…However, there is only limited evidence that opioids modulate neurotransmitter uptake. For instance, morphine, methadone, codeine and thebaine reduced [ 3 H]noradrenaline uptake in rabbit brain synaptosomes [2]. Similarly, methadone and morphine reduced [ 3 H]5-hydroxytryptamine uptake in rat brain synaptosomes, but only methadone reduced [ 3 H]noradrenaline uptake [3].…”

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confidence: 98%

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Fentanyl Inhibits the Uptake of [ 3 H]noradrenaline in Cultured Neuronal Cells

Atcheson

Rowbotham

Lambert

1993

British Journal of Anaesthesia

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We have examined how fentanyl modulates [3H]noradrenaline uptake in two cultured neuronal cell preparations, the human neuroblastoma SH-SY5Y and the rat phaeochromocytoma PC12. Fentanyl produced a significant, dose-dependent inhibition of [3H]noradrenaline uptake at concentrations in excess of 0.1 mumol litre-1 (P < 0.05) and 0.3 mumol litre-1 (P < 0.05) for PC12 and SH-SY5Y cells, respectively. However, these values exceed the serum concentration of fentanyl required to produce analgesia. At the maximum concentration examined (100 mumol litre-1), fentanyl produced 85-95% inhibition of uptake. This effect was not antagonized by naloxone, implying a nonopioid mechanism of action. Imipramine 1 mumol litre-1 reduced [3H]noradrenaline uptake by 65-70% but morphine, in contrast to fentanyl, had no effect (P > 0.1).

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 98%

Fentanyl Inhibits the Uptake of [ 3 H]noradrenaline in Cultured Neuronal Cells

Atcheson

Rowbotham

Lambert

1993

British Journal of Anaesthesia

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“…Since the concentrations of morphine required for this effect do not affect noradrenaline uptake into peripheral (Montel & Starke, 1973) or central neurones (Ciofalo, 1972), morphine would appear to act on the noradrenergic nerve terminals to decrease transmitter release. The nictitating membrane may be added to the relatively few tissues with autonomic innervation in which a specific morphine receptor has been demonstrated.…”

Section: Discussionmentioning

confidence: 99%

“…The inhibition of noradrenaline output from the cat nictitating membrane by morphine is due to a stereospecific effect at a morphine receptor site because the inhibitory effects are reversed by naloxone, and levorphanol has a much greater depressant effect than its dextro-isomer, dextrorphan. Since the concentrations of morphine required for this effect do not affect noradrenaline uptake into peripheral (Montel & Starke, 1973) or central neurones (Ciofalo, 1972), morphine would appear to act on the noradrenergic nerve terminals to decrease transmitter release. The nictitating membrane may be added to the relatively few tissues with autonomic innervation in which a specific morphine receptor has been demonstrated.…”

Section: Discussionmentioning

confidence: 99%

The Effects of Morphine on the Release of Noradrenaline From the Cat Isolated Nictitating Membrane and the Guinea‐pig Ileum Myenteric Plexus‐longitudinal Muscle Preparation

Henderson

Hughes

Kosterlitz

1975

British J Pharmacology

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Electrical field stimulation of either the cat isolated nictitating membrane or the guinea‐pig ileum myenteric plexus‐longitudinal muscle preparation caused the release of noradrenaline into the bathing medium. In the cat nictitating membrane, the output per pulse of noradrenaline was constant at frequencies of stimulation from 0.5 to 15 Hz. In the guinea‐pig myenteric plexus preparation the output per pulse of noradrenaline increased as the frequency of stimulation was increased from 2 to 16 Hz. Phenoxybenzamine (29.3 μM) caused a marked increase in the noradrenaline output from both the cat nictitating membrane and guinea‐pig myenteric plexus preparations. Morphine (0.13‐8 μM) inhibited the contractions of the cat nictitating membrane caused by electrical stimulation. This effect was greater at low (1 Hz) than at high (15 Hz) frequencies of stimulation. The site of action is at the nerve‐smooth muscle junction. The action of narcotic analgesic drugs on the cat nictitating membrane showed stereospecificity. Naloxone (0.1 μM) reversed the inhibition caused by normorphine (3.2 μM). Morphine (3 μM) reduced the noradrenaline output from the cat nictitating membrane stimulated at 1 Hz but not at 15 Hz. At 1 Hz, the inhibition of noradrenaline output by normorphine (5 μM) was reversed by naloxone (0.25 μM). Morphine (1.5 μM) did not alter the noradrenaline output from the guinea‐pig myenteric plexus preparation stimulated at 2 or 16 Hz.

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“…It is conceivable that microiontophoretically applied morphine might act on specific neuronal receptors and it would therefore be of interest to know whether the excitation or inhibition of neurones could be mimicked by other opiates and blocked by morphine antagonists. Acute administration of morphine has been shown to release noradrenaline from the brain (Gunne, 1959), increase noradrenaline turnover in the brain stem (Sugrue, 1973) and inhibit its uptake (Ciofalo & Lucero, 1972).…”

Section: Discussionmentioning

confidence: 99%

Morphine and Neurotransmitter Substances: Microiontophoretic Study in the Rat Brain Stem

Bradley¹,

Dray

1974

British J Pharmacology

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The effects of microiontophoretically applied morphine and its interactions with the effects of microiontophoretic applications of either acetylcholine, (–)‐noradrenaline or 5‐hydroxytryptamine have been studied on single neurones in the brain stem of rats anaesthetized with urethane. Morphine excited or inhibited most neurones tested and the effects, especially excitation, were often extremely powerful. However, the time course of the excitatory and inhibitory effects were somewhat different. Desensitization to the excitation produced by morphine was seen after repeated or prolonged applications and it is suggested that this phenomenon may be related to the tolerance which develops after chronic administration of morphine. No desensitization was observed to inhibition of neuronal activity by morphine. Morphine usually reduced the excitation of neurones by acetylcholine, noradrenaline or 5‐hydroxytryptamine but sometimes potentiated the effect, although not always on the same neurones. Inhibition of neuronal activity by these compounds was never modified by morphine and neither were the effects of glutamate or D,L‐homocysteic acid when used as control agonists. The in vitro release of morphine from six micropipettes was determined and the transport number was calculated to be 0.051 (s.d. 0.021). The implications of these observations in explaining the pharmacological actions of morphine are discussed.

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Effects of some narcotics and antagonists on synaptosomal 3H-norepinephrine uptake

Cited by 23 publications

References 5 publications

Fentanyl Inhibits the Uptake of [ 3 H]noradrenaline in Cultured Neuronal Cells

Fentanyl Inhibits the Uptake of [ 3 H]noradrenaline in Cultured Neuronal Cells

The Effects of Morphine on the Release of Noradrenaline From the Cat Isolated Nictitating Membrane and the Guinea‐pig Ileum Myenteric Plexus‐longitudinal Muscle Preparation

Morphine and Neurotransmitter Substances: Microiontophoretic Study in the Rat Brain Stem

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