Opioid peptides and glucose metabolism.
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Animals↗
Biomedical subjects
P Bouloux
Publications and source records attributed to P Bouloux.
Alpha-adrenergic stimulation of corticotropin secretion by a specific central mechanism in man.
In a double-blind study in normal subjects, methoxamine, a highly selective agonist at alpha-1-adrenoceptors, significantly increased circulating ACTH and cortisol. The stimulant effect of methoxamine on cortisol secretion was dose dependent in the range 3.5-7 micrograms/kg/min, was abolished by concomitant administration of the strong alpha-1-adrenergic (and weak H1) antagonist thymoxamine but unaffected by the antihistamine, chlorpheniramine. In order to test whether the action of methoxamine on ACTH secretion was exerted centrally or peripherally, the effects of norepinephrine (NE), an alpha-1-agonist that does not cross the blood-brain barrier, were studied. Doses of NE (1-12 micrograms/min) that increased systolic blood pressure by amounts similar to the changes produced by methoxamine, did not result in any rise in plasma cortisol in normal subjects. The effect of methoxamine, which is more lipid soluble than NE, on plasma ACTH and cortisol, appears to be exerted on the CNS and not at the pituitary or via nonspecific peripheral mechanisms. In addition to its water solubility, NE differs from methoxamine in its beta-1-, beta-2- and alpha-2-agonist actions. However, prenalterol (2 mg) and salbutamol (250 micrograms), respectively beta-1- and beta-2-adrenergic agonist drugs, had no effect on the secretion of ACTH or cortisol and the alpha-2-antagonist yohimbine in an effective dose did not unmask a stimulant effect of intravenous NE on plasma cortisol. At high infusion rates, NE significantly inhibited cortisol secretion. Stimulation of central alpha-1-adrenergic mechanisms results in secretion of ACTH in man, presumably by increased release of a corticotropin-releasing factor.
Adrenocorticotropic Hormone↗
Effect of an opiate antagonist on the responses of circulating catecholamines and the renin-aldosterone system to acute sympathetic stimulation by hand-grip in man.
The effect of naloxone on the neurohumoral responses to acute sympathetic stimulation by sustained hand-grip in normal man was investigated. Six normal males were studied fasting at 08.30 h, on two occasions at 7-day intervals, with each subject sustaining 30% of his maximal hand-grip on a hand dynamometer for 5 min. Naloxone (8 mg bolus) in 20 ml normal saline, or saline alone, was given 5 min before hand-grip in a randomised double-blind cross-over trial. Blood was sampled for plasma renin activity, serum aldosterone and plasma catecholamines. The study was repeated in the absence of hand-grip. Sustained hand-grip produced significant elevations in mean blood-pressure, circulating adrenaline, noradrenaline and aldosterone. Naloxone, which had no effect on basal catecholamines, plasma renin activity or aldosterone, significantly enhanced the responses in plasma adrenaline, plasma renin activity and serum aldosterone to hand-grip. The increments in blood pressure and noradrenaline were not affected. These results suggest that endogenous opioids modulate the response of the sympathoadrenal and renin-aldosterone systems to acute sympathetic stimulation by a mild stress in man.
Adult↗
The relationship between serum prolactin and immunocytochemical staining for prolactin in patients with pituitary macroadenomas.
We have studied the relationship between mean pretreatment levels of serum prolactin and the presence of positive immunohistochemical staining for prolactin in the pituitary tumours of 55 patients. Pretreatment serum prolactin was significantly higher in patients with tumours showing many prolactin immunostaining cells than in those with none (P less than 0.001). When the pretreatment serum prolactin exceeded 6000 mU/l, the tumours contained over 90% of prolactin positive cells; one patient was an exception who had received long-term high dose bromocriptine therapy, and her tumour showed only occasional cells with positive staining. When the pretreatment serum prolactin level was under 2500 mU/l, a tumour was found which showed either no cells or fewer than 1% of cells which stained for prolactin. There was no significant difference in pretreatment serum prolactin levels between 11 patients with craniopharyngiomas and 34 patients with pituitary macroadenomas showing no prolactin immunostaining. Seventy-one percent (32) of the 45 patients with craniopharyngiomas or tumours with negative immunostaining for prolactin, had raised pretreatment serum prolactin levels (above 360 mU/l) although this was usually only slightly elevated; the levels exceeded 2500 mU/l in six (13%) of them (two craniopharyngiomas, four pituitary tumours) but in none did the levels exceed 6000 mU/l. Four of the 55 pituitary tumours showed occasional cells (less than 1%) that stained positively for growth hormone. In none of the patients with these tumours was there evidence of acromegaly or pathologically elevated circulating growth hormone levels.
Adenoma↗
Methodological considerations in the determination of plasma catecholamines by high-performance liquid chromatography with electrochemical detection.
We report on a systematic investigation into some frequently encountered problems in the estimation of catecholamines in plasma and biological fluids using high-performance liquid chromatography with electrochemical detection. The kinetics of adsorption and desorption of catecholamines from plasma on to alumina has been studied using laboratory-prepared and some commercial aluminas with various acids. Chromatographic conditions yielding optimal resolution and sensitivity have been characterised. Some possible interfering peaks have been identified. The stability of catecholamines in plasma has been studied.
Adolescent↗
Sympathoadrenal function during cardiac operations in infants with the technique of surface cooling, limited cardiopulmonary bypass, and circulatory arrest.
The sympathoadrenal response to surface cooling, limited cardiopulmonary bypass, and deep hypothermic circulatory arrest was investigated in 22 infants undergoing correction of congenital heart defects. Surface cooling to 26 degrees C was associated with a significant rise in plasma epinephrine and norepinephrine levels. Both levels fell during the period of core cooling on bypass, presumably because of hemodilution. Following the period of circulatory arrest there was a rise in both catecholamine levels that correlated nonlinearly with the duration of circulatory arrest. The catecholamine levels remained high after rewarming until the chest was closed. The results suggest that this type of surgical procedure produces severe sympathoadrenal stress. The extremely high values found in the postarrest period in some patients, who had had a long period of arrest (greater than 40 minutes), may indicate hypoxic stress. The biological effect of high circulating plasma catecholamines during hypothermia is difficult to assess. The heart rate response to plasma catecholamine levels tended to diminish on cooling in our patients.
Cardiopulmonary Bypass↗
The role of opioid peptides in the hormonal responses to acute exercise in man.
Opioid involvement in the physiological and hormonal responses to acute exercise was investigated in six normal male subjects. Each was exercised to 40% (mild exercise) and 80% (severe exercise) of his previously determined maximal oxygen consumption on two occasions, with and without an infusion of high-dose naloxone. The exercise task was a bicycle ergometer; mild and severe exercise were performed for 20 min each, followed by a recovery period. Exercise produced the expected increases in heart rate, blood pressure, ventilation, tidal volume, respiratory rate, oxygen consumption and carbon dioxide production. After severe exercise, naloxone infusion increased ventilation from 94.8 +/- 4.9 litres/min to 105.7 +/- 5.0 litres/min (P less than 0.05), but had no effect on any of the other physiological variables. Exercise-induced changes in several hormones and metabolites were noted, including elevations in circulating lactate, growth hormone (GH), prolactin, cortisol, luteinizing hormone (LH), follicle stimulating hormone (FSH), adrenaline noradrenaline, plasma renin activity (PRA) and aldosterone. There was no change in plasma met-enkephalin. Naloxone infusion produced the expected increases in LH and cortisol, but also significantly enhanced the elevations in prolactin, adrenaline, noradrenaline, plasma renin activity and aldosterone (P less than 0.05). Psychological questionnaires revealed minor mood changes after exercise, but no evidence was found for the suggested 'high' or euphoria of exercise. Effort was perceived as greater during the naloxone infusion than the saline infusion in every subject.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Imaging of phaeochromocytoma and adrenal medulla with 123I-meta-iodobenzyl guanidine.
A method for preparing meta-iodobenzyl guanidine (MIBG) labelled with 123I is described. This compound clearly imaged the normal adrenal medulla in seven out of eight patients with hypertension. The sites of metastases were demonstrated in two patients with malignant phaeochromocytoma.
3-Iodobenzylguanidine↗
Effect of the dopamine agonist, lergotrile mesylate, on circulating anterior pituitary hormones in man.
The effects of the ergoline derivative, lergotrile mesylate, on the serum levels of PRL, GH, TSH, LH, FSH, cortisol, and blood sugar were studied in six normal males. The effects of lergotrile mesylate on the serum levels of GH and PRL were also studied in eight patients with acromegaly and in two with idiopathic hyperprolactinemia. In the normal subjects, 2 mg oral lergotrile lowered basal PRL levels after 90 min and markedly impaired the PRL response to TRH (200 micrograms iv); the mean peak value +/- SE was 8.3 +/- 1.1 micrograms/liter, compared to the control value of 66.6 /+- 11.3 micrograms/liter. Lergotrile raised serum GH levels in five of the six subjects to peaks of 8-49 micrograms/liter, compared to 2-8 micrograms/liter after placebo. In three subjects, the GH response to lergotrile was attenuated by the prior administration of the dopamine antagonist, metoclopramide (10 mg orally). Lergotrile had no effect on FSH and LH levels under basal conditions or after the gonadotrophin-releasing hormone (GnRH; 100 micrograms iv). Circulating TSH levels were unaltered basally but impaired after TRH. Blood sugar levels were unaltered; serum cortisol was elevated in five of six subjects; there was a brief depression of diastolic blood pressure, but no change in pulse rate. The side effects after lergotrile were variable, with drowsiness as a consistent feature. These actions are similar to those of bromocriptine (an ergot derivative treatment of hyperprolactinemia and acromegaly, to suppress PRL and GH secretion, and in parkinsonism. Therefore, it may be expected that lergotrile could fulfill these clinical uses; however, in the studies comparing the effects of single oral doses of lergotrile (2 mg) and bromocriptine (2.5 mg) on GH and PRL secretion in patients with acromegaly and hyperprolactinemia, lergotrile in the dose used has been found to have an earlier onset and shorter duration of action.
Acromegaly↗