Beta-blocker withdrawal syndrome.
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Biomedical subjects
Publications and source records attributed to A Gibson.
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1. The effects of opioid drugs and of Na+ replacement on steroidogenesis in rat adrenal cell suspensions were investigated. 2. In medium containing normal Na+ (156 mM), opioid antagonists but not opioid agonists reduced the steroidogenic response to adrenocorticotrophic hormone1-24 (ACTH1-24) but not to dibutyryl adenosine 3',5' cyclic monophosphate (db cyclic AMP). 3. Replacement of 50% Na+ in the medium by choline had no effect on steroidogenesis, but further reductions in Na+ content reduced the steroidogenic activity of both ACTH1-24 and db cyclic AMP. 4. In 50% Na+ medium both opioid agonists and antagonists inhibited ACTH1-24 induced steroidogenesis. 5. Addition of therapeutic concentrations of lithium to otherwise normal medium inhibited the steroidogenic response to ACTH1--24 but not to db cyclic AMP. 6. The selective inhibition of ACTH1--24-induced steroidogenesis by opioid drugs suggests some similarity between the opioid and ACTH receptors. 7. The relevance of the potent inhibitory effect of lithium to its therapeutic actions is discussed.
Ether stress or intracerebroventricular (i.c.v.) administration of saline, met-enkephalin, or naltrexone raised plasma corticosterone levels in mice. The response to ether stress was abolished by a preceding ether stress or by pretreatment with i.c.v. saline or naltrexone. However, following i.c.v. met-enkephalin, plasma corticosterone was significantly elevated by ether stress, the effect being blocked by simultaneous injection of met-enkephalin and naltrexone. Met-enkephalin appears to prevent fast-feedback inhibition of the hypothalamus-pituitary-adrenal system.
1 Intraperitoneal administration of normorphine, morphine or naloxone or exposure to ether vapour for 1 min, elevated plasma corticosteroid concentrations in mice. 2 Injection of saline or exposure to ether vapour rendered mice less sensitive to a subsequent exposure to ether vapour 15 min later. 3 Treatment with normorphine (50 mg/kg) potentiated the corticosteroid response to ether stress whilst pentazocine (20 mg/kg), naltrexone (10 mg/kg), morphine (24 mg/kg), levorphanol (20 mg/kg) and naloxone (50 mg/kg) prevented the stress-induced elevation of plasma corticosteroids. 4 Both naloxone and morphine inhibited the potentiation by normorphine of the response to ether, the dose of naloxone required being higher than that for inhibition of normorphine analgesia. 5 It is concluded that endogenous opioid peptides may be involved in the control of the response to ether stress in mice.
Noradrenaline (NA) and dopamine (DA) contracted the mouse vas deferens and reduced the responses to low frequency nerve stimulation (0.1 Hz). The relative potencies of antagonists suggested that these effects were due to stimulation of post-synaptic and pre-synaptic alpha-adrenoceptors respectively. Bromocriptine produced a non-competitive antagonism of contractile responses to NA (pD2' = 7.6) and DA (pD2' = 8.0) but had no effect on responses to carbachol. Bromocriptine also reduced single twitch responses of the vas to low frequency field stimulation (0.1 Hz), but did not affect stimulation at higher frequencies (1--20 Hz). Yohimbine selectively and rapidly reversed the inhibiting effects of bromocriptine on single twitches, although they could not easily be reversed by washing. Bromocriptine produced a yohimbine-reversible reduction in the stimulated overflow of tritium from vasa previously loaded with 3H--NA. Thus the mouse vas deferens does not appear to contain specific DA receptors and the results suggest that bromocriptine acts as a pre-synaptic alpha-adrenoceptor agonist and post-synaptic alpha-adrenoceptor antagonist in this tissue.
1. The effect of restricted water intake followed by voluntary rehydration with water or 10 mM-KCl was studied in four conscious sheep with respect to plasma concentrations of renin, antidiuretic hormone (ADH), protein and electrolytes, and urine flow rate, osmolality and osmolal excretion. 2. Water restriction increased the plasma renin concentration and the plasma ADH concentration. 3. Rehydration with water caused a further rise in plasma renin, but plasma ADH returned to basal levels in less than 2 hr. 4. Rehydration with 10 mM-KCl in order to stabilize plasma K concentration greatly attenuated the post-drinking rise in plasma renin concentration, while plasma ADH levels fell as before. 5. Urine flow rates after rehydration with water and 10 mM-KCl remained low for at least 6 hr in most experiments despite low plasma ADH levels. The effect on urine osmolality ranged from no change to a large drop. 6. The post-drinking antidiuresis was associated with a reduction in solute excretion rate. However, free water clearance usually remained negative. 7. These experiments do not support the existence of a direct nexus between plasma ADH levels and plasma renin concentration.
1. The superior colliculus projects to the dorsolateral nucleus of the pons. Retrograde transport of horseradish peroxidase (HRP) revealed that cells in the superior colliculus, which send their axons to the pons, lie in both superficial (III) and deep (IV--VII) layers. Superficial cells outnumbered deep cells. The inferior colliculus also projects heavily to the dorsolateral pontine nucleus. 2. Dorsolateral pontine visual cells were activated only by visual stimulation. Cells responsive to somatic or auditory stimulation were also found in the dorsolateral nucleus, and they too responded to only one sense modality. 3. Of the dorsolateral pontine visual cells, 69% were directionally selective. 4. Dorsolateral pontine visual cells were responsive to moving targets over a wide range of stimulus velocities. Velocities between 25 and 100 degrees/s were the most effective. No cells responded to a stationary stimulus. 5. Single-spot targets were the most effective stimuli. Stimulus size was a more important parameter than stimulus configuration. Many cells had inhibitory regions outside of their excitatory fields. 6. The excitatory receptive fields of dorsolateral pontine cells were very large (median, 1,100 deg2). 7. Nearly all receptive fields were centered in the contralateral visual hemifield, and 91% of the dorsolateral visual cells were activated from either eye. 8. We conclude that the visual cells in the dorsolateral nucleus have receptive-field properties that are similar to those of cells in the superior colliculus. The preference of dorsolateral cells for single-spot targets contrasts strongly with the multiple-spot preference of medial pontine cells, which receive their input from visual cortex.
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Technetium polyphosphate uptake by breast tumours has been investigated in 69 patients. Although 70 per cent (38 out of 54) of malignant tumours took up the isotope in comparison with 45 per cent (5 out of 11) of benign lesions, this technique would be unreliable for diagnostic purposes.
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1. Area 18 projects to the rostral pontine nuclei. The visual response properties of rostral pontine cells differ greatly from those that have been reported for area 18 cells. We identified and studied corticopontine cells in area 18 and compared their receptive-field properties to those of other area 18 cells and to pontine visual cells. 2. We first located the visual area in the rostral pons by microelectrode recording and placed stimulating electrodes at the same site. Anti-dromically invaded cells were then recorded in area 18. The antidromic invasion of each cell was verified by orthodromic-antidromic spike collision. 3. Fifty-seven well-isolated corticopontine cells were studied in detail. We also recorded 466 unitary antidromic potentials with a mean invasion latency of 3.5 ms and recorded from 40 additional area 18 units to serve as a comparison group for the corticopontine cells. The comparison group cells were located in the same area in the visual field as the corticopontine cells. 4. The average receptive-field area for corticopontine cells (485 deg2) was much larger than the comparison cells (59 deg2). Forty percent of the corticopontine cells responded preferentially to multiple-spot target. Properly oriented gratings, slits, or edges were the most effective stimuli for the comparison cells. Eighty-two percent of the corticopontine cells showed clear directional preferences to moving-spot stimuli, and downward movements were most commonly preferred. Fifty-five percent of the area 18 comparison cells showed some directional preference, but no particular direction was preferred. The optimal stimulus speeds for corticopontine cells were higher than those for the comparison cells. 5. The response properties of the area 18 corticopontine cells are similar to the response properties of rostral pontine visual cells, except for a somewhat higher selectivity for orientation in the corticopontine cells. 6. We conclude that most response properties of rostral pontine visual cells are already present in a subset of area 18 cortical cells which project to the pons. The corticopontine cells are sensitive to multiple-spot targets moving in particular directions over large portions of the visual field, such properties are consistent with a visuomotor function for the corticopontocerebellar pathway.
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The effect of testosterone and of castration on the contractility of the rat anococcygeus muscle, on plasma corticosterone concentrations, and on adrenal gland weights, was investigated. Castration was without effect on smooth muscle reactivity. However, testosterone increased muscle contractility to both NA and ACh, when given to control or castrated rats. Castration reduced both plasma corticosterone and adrenal gland weight, and this effect could be reversed by testosterone. It is concluded that changes in circulating testosterone levels cannot explain the lack of effect of adrenalectomy on muscle contractility. The possible mechanism of action of testosterone is discussed.
1. The nature of KCl-induced relaxations of the rat anococcygeus muscle was investigated. 2. The relaxations were mimicked by other K+ salts, but not by NaCl. 3. The muscle was more susceptible to the relaxant effects of KCl than the contractile effects. 4. Addition of ouabain (100 micron) had no effect on the relaxations. 5. The relaxations were abolished by tetrodotoxin (5 microgram/ml), procaine (500 micron), and by section of the inhibitory nerves. 6. The results suggest that KCl-induced relaxations are due to stimulation of the inhibitory nerves by K+.
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