Effect of morphine and naloxone on priming-induced audiogenic seizures in BALB/c mice.
(1/2575)
1 Morphine (1-200 mg/kg s.c.) reduced the incidence and prolonged the latency of priming-induced audiogenic siezures in a dose-dependent manner. 2 This effect was reversed by naloxone (1 and 2 mg/kg) although naloxone was itself inactive. 3 This priming-induces seizure model may be useful in the study of tolerance and physical dependence. (+info)
Long-term effects of N-2-chlorethyl-N-ethyl-2-bromobenzylamine hydrochloride on noradrenergic neurones in the rat brain and heart.
(2/2575)
1 N-2-Chlorethyl-N-ethyl-2-bromobenzylamine hydrochloride (DSP 4) 50 mg/kg intraperitoneally, produced a long-term decrease in the capacity of brain homogenates to accumulate noradrenaline with significant effect 8 months after the injection. It had no effect on the noradrenaline uptake in homogenates from the striatum (dopamine neurones) and on the uptake of 5-hydroxytryptamine (5-HT) in various brain regions. 2 In vitro DSP 4 inhibited the noradrenaline uptake in a cortical homogenate with an IC50 value of 2 muM but was more than ten times less active on the dopamine uptake in a striatal homogenate and the 5-HT uptake in a cortical homogenate. 3 DSP 4 (50 mg/kg i.p.) inhibited the uptake of noradrenaline in the rat heart atrium in vitro but this action was terminated within 2 weeks. 4 DSP 4 (50 mg/kg i.p.) cuased a decrease in the dopamine-beta-hydroxylase (DBH) activity in the rat brain and heart. The onset of this effect was slow; in heart a lag period of 2-4 days was noted. In brain the DBH-activity in cerebral cortex was much more decreased than that in hypothalamus which was only slightly affected. A significant effect was still found 8 months after the injection. The noradrenaline concentration in the brain was greatly decreased for at least two weeks, whereas noradrenaline in heart was only temporarily reduced. 5 The long-term effects of DSP 4 on the noradrenaline accumulation, the DBH activity and noradrenaline concentration in the rat brain were antagonized by desipramine (10 mg/kg i.p.). 6 It is suggested that DSP 4 primarily attacks the membranal noradrenaline uptake sites forming a covalent bond and that the nerve terminals, as a result of this binding, degenerate. (+info)
Inhibition by amiloride of sodium-dependent fluid reabsorption in the rat isolated caudal epididymis.
(3/2575)
The rate of fluid reabsorption was studied in the rat isolated caudal epididymal sac in vitro. 2 Part of the fluid reabsorption was found to be dependent on intraluminal Na+. Amiloride (0.1 mM) completely inhibited this component of fluid reabsorption. 3 The log dose-inhibition curve to amiloride was sigmoid and the IC50 value was found to be 1.6 muM. (+info)
Further evidence that prostaglandins inhibit the release of noradrenaline from adrenergic nerve terminals by restriction of availability of calcium.
(4/2575)
1 Guinea-pig vasa deferentia were continuously superfused after labelling the transmitter stores with [3H](-)-noradrenaline. Release of [3H]-(-)-noradrenaline was induced by transmural nerve stimulation. 2 Prostglandin E2 (14 nM) drastically reduced the release of [3H]-(-)-noradrenaline, while tetraethylammonium (2 mM), rubidium (6 mM), phenoxybenzamine (3 muM) each in the presence or absence of Uptake 1 or 2 blockade, and prolonged pulse duration (from 0.5 to 2.0 ms) all significantly increased the release of [3H]-(-)-noradrenaline per nerve impulse. 3 The inhibitory effect of prostaglandin E2 on evoked release of [3H]-(-)-noradrenaline was significantly reduced by tetraethylammonium, rubidium and prolonged pulse duration, whilst it was actually enhanced by phenoxybenzamine. This indicates that increased release of noradrenaline per nerve impulse does not per se counteract the inhibitory effect of prostaglandin E2. 4 It is concluded that tetraethylammonium, rubidium and prolonged pulse duration counteracted the inhibitory effect of prostaglandin E2 on T3H]-(-)-noradrenaline release by promoting calcium influx during the nerve action potential. The results are consistent with, and add more weight to the view that prostaglandins inhibit the release of noradrenaline by restriction of calcium availability. (+info)
Possible suppression of host resistance by estrogen therapy for prostatic cancer.(5/2575)
Evaluation of the force-frequency relationship as a descriptor of the inotropic state of canine left ventricular myocardium.
(6/2575)
The short-term force-frequency characteristics of canine left ventricular myocardium were examined in both isolated and intact preparations by briefly pertubing the frequency of contraction with early extrasystoles. The maximum rate of rise of isometric tension (Fmas) of the isolated trabeculae carneae was potentiated by the introduction of extrasystoles. The ratio of Fmas of potentiated to control beats (force-frequency ratio) was not altered significantly by a change in muscle length. However, exposure of the trabeculae to isoproterenol (10(-7)M) significantly changed the force-frequency ratio obtained in response to a constant frequency perturbation. Similar experiments were performed on chronically instrumented conscious dogs. Left ventricular minor axis diameter was measured with implanted pulse-transit ultrasonic dimension transducers, and intracavitary pressure was measured with a high fidelity micromanometer. Atrial pacing was performed so that the end-diastolic diameters of the beats preceding and following the extrasystole could be made identical. Large increases in the maximum rate of rise of pressure (Pmas) were seen in the contraction after the extrasystole. The ratio of Pmax of the potentiated beat to that of the control beat was not changed by a 9% increase in the end-diastolic diameter, produced by saline infusion. Conversely, isoproterenol significantly altered this relationship in the same manner as in the isolated muscle. Thus, either in vitro or in situ, left ventricular myocardium exhibits large functional changes in response to brief perturbations in rate. The isoproterenol and length data indicate that the force-frequency ratio reflects frequency-dependent changes in the inotropic state, independent of changes in length. (+info)
Effect of paracetamol (acetaminophen) on gastric ionic fluxes and potential difference in man.
(7/2575)
Paracetamol has replaced aspirin as the analgesic of choice in many situations. The major reason is the damaging effect of aspirin on gastric mucosa. Alterations in gastric ionic fluxes and potential difference provide measures of aspirin-induced structural damage. We studied the effect of large doses of paracetamol (acetaminophen 2-0 g) on gastric ionic fluxes in man. In addition, the effect of 2-0 g paracetamol on gastric potential difference was compared with that of 600 mg aspirin. In contrast with salicylates, paracetamol caused no significant alteration in movement of H+ and Na+ ions over control periods. Aspirin causes a significant fall in transmucosal potential difference (PD) across gastric mucosa of 15 mv, while paracetamol cuased no significant change. Paracetamol in a dose four times that recommended does not alter gastric ionic fluxes or potential difference. These studies support choice of paracetamol as analgesic over aspirin where damage to gastric mucosa may be critical. (+info)
Acute conduction velocity changes in guinea-pigs after administration of diphenylhydantoin.
(8/2575)
Motor nerve conduction velocity was measured after dosing guinea-pigs with 200-400 mumol/kg diphenylhydantoin (DPH) daily for three to four days. Conduction velocity fell by a mean value of 13% in animals that achieved plasma DPH levels over 200 mumol/l. There was no change in velocity with DPH levels below this value. (+info)