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Biomedical subjects

V Clement-Jones

Publications and source records attributed to V Clement-Jones.

At least 19 recordsLinked to original sources
PubMed1983

Opiate receptors: enkephalins and endorphins.

Opiate receptors in the central nervous system may be classified according to pharmacological, behavioural, or binding studies. Classical mu-receptors probably have beta-endorphin as an endogenous ligand, and seem to be involved in the modulation of pain perception, low-frequency acupuncture analgesia, and the stimulation of prolactin, growth hormone and thyroid-stimulating hormone release. Met-enkephalin is likely to be an endogenous ligand for the delta-receptors, which predominate in the basal ganglia and limbic systems; such receptors may tonically inhibit the release of corticotrophin-releasing factor. It has been suggested that the newly-described kappa-receptors may inhibit the release of vasopressin and gonadotrophin-releasing factor; dynorphin may be their endogenous ligand. Endogenous opiates controlling cardiovascular and respiratory reflexes are likely to activate mu-receptors, while high-frequency acupuncture may alleviate the symptoms of opiate withdrawal by allowing an increase in Met-enkephalin to activate delta-receptors. In the periphery, beta-endorphin is concentrated in the corticotrophs of the anterior pituitary, and is cosecreted with ACTH and related peptides. Circulating Met-enkephalin originates in the gut, sympathetic nervous system and adrenal medulla. Met-enkephalin may also be extracted from carcinoid tumours and phaeochromocytomas. Elevations in circulating Met-enkephalin may occur in certain disease states with cardiovascular and psychiatric manifestations. However, manipulation of endogenous or exogenous opiates has as yet no certain place in any clinical situation.

Acupuncture Therapy↗
PubMed1982

Simultaneous release of neurotensin, somatostatin, enkephalins and catecholamines from perfused cat adrenal glands.

Acid extracts of cat adrenal medullae were found to contain neurotensin-like (0.71 +/- 0.21nmol/gm), met-enkephalin-like (11.71 +/- 2.87nmol/gm), leu-enkephalin-like (1.95 +/- 0.11nmol/gm) and somatostatin-like (1.57 +/- 0.63pmol/gm) immunoreactivities. Using isolated retrogradely perfused cat adrenal glands the secretory responses to acetylcholine (ACh), nicotine and potassium ions (K+) were studied. Spontaneous secretion of catecholamines, neurotensin-like, met-enkephalin-like, leu-enkephalin-like and somatostatin-like immunoreactivities was negligible. However, ACh (5.5 X 10(-5)M), nicotine (2.2 X 10(-5)M) and 55mM K+ all evoked the simultaneous release of noradrenaline, adrenaline and the four neuropeptide immunoreactivities. The ACh stimulated secretion of the four neuropeptides could be prevented by perfusion with hexamethonium (C6, 2.8 X 10(-4)M). The concomitant release of these neuropeptides with catecholamines suggests that they may have a role in the modulation of stress responses.

Acetylcholine↗
PubMed1981

Chlorpropamide alcohol flush and circulating met-enkephalin: a positive link.

Chlorpropamide-alcohol flushing may be due to sensitivity to endogenous opiates. To investigate this possibility the plasma met-enkephalin and beta-endorphin responses to sherry with and without chlorpropamide were studied in six patients with non-insulin dependent diabetes and in six normal subjects. After chlorpropamide all patients showed a rise in met-enkephalin concentrations from a basal level of 50 +/- 7.2 ng/l to a peak of 75 +/- 8.1 ng/l (p less than 0.001). In contrast, before chlorpropamide treatment was started met-enkephalin values did not change after alcohol. No significant changes in beta-endorphin values were observed. In six normal subjects pretreated with chlorpropamide the met-enkephalin concentration also rose from a basal level of 72 +/- 15 ng/l to a peak of 103 +/- 9.4 ng/l (p less than 0.002). Again, the met-enkephalin rise was not observed after placebo. Neither beta-endorphin concentrations nor facial temperature changed significantly. These data suggest that endogenous opiates may be implicated in CPAF. Furthermore, this is the first study in which a significant change in circulating met-enkephalin values has occurred.

Chlorpropamide↗
PubMed1981

A study of 24-hour profiles of plasma met-enkephalin in man.

Met-enkephalin has recently been demonstrated to circulate in human plasma and using this highly specific extracted radioimmunoassay the fluctuations of plasma Met-enkephalin in man were studied over 24 h. The subjects were 6 healthy volunteers. Following a 24 h adaptation period in the metabolic ward and sleep laboratory, an i.v. catheter was inserted. Blood samples were taken at hourly intervals through the day and at 30 min intervals between 23.00 h and 07.00 h. Sleep was monitored polygraphically. There was no regular rhythm discernible in plasma Met-enkephalin levels throughout the 24 h, nor was there any relationship with sleep or food intake. In a further 3 subjects beta-LPH and beta-endorphin levels as estimated by N- and C-terminal beta-LPH radioimmunoassay were elevated on waking compared with 01.00 h, suggesting a nyctohemeral rhythm. In contrast to the correlated circadian fluctuations in beta-LPH, ACTH and beta-endorphin levels therefore, the lack of circadian rhythmicity and dissociation of plasma Met-enkephalin from plasma levels of the former group of peptides suggests control mechanisms for the secretion of Met-enkephalin are quite different and adds support to the concept of separate Met-enkephalin precursors.

Adrenocorticotropic Hormone↗
PubMed1981

Pars intermedia peptides: studies in adult humans.

A combination of radioimmunoassays and chromatography under acid-dissociating conditions has been used to obtain profiles of ACTH and LPH-related peptides in human plasma and cerebrospinal fluid. The spectra of peptides observed in these two fluids differ markedly. ACTH, beta-LPH, gamma-LPH and beta-endorphin are observed in the plasma of normal subjects and patients with increased pituitary ACTH secretion, whereas cerebrospinal fluid contains ACTH, beta-LPH, gamma-LPH and beta-endorphin, a 31 000-molecular-weight putative precursor having ACTH, LPH and gamma-MSH immunoreactivities, as well as pro-gamma-MSH(1-77) and smaller immunoreactive gamma-MSH fragments, alpha-MSH was not observed in blood or cerebrospinal fluid but this pars intermedia peptide and corticotropin-like intermediate lobe peptide (CLIP) were both found in tumour tissues obtained from patients with the ectopic ACTH syndrome. In vitro studies of human pituitary tumour tissues confirmed concomitant secretion of ACTH, beta-LPH, gamma-LPH, beta-endorphin and pro-gamma-MSH, which could be stimulated by a preparation of crude stalk median eminence and synthetic arginine vasopressin, from the rat, and could be suppressed by hydrocortisone. Clinical studies in which electroacupuncture was used to alleviate the symptoms of heroin withdrawal or recurrent pain revealed that concentrations of met-enkephalin and beta-endorphin, respectively, may rise in cerebrospinal fluid in association with relief of symptoms.

Adrenocorticotropic Hormone↗
PubMed1980

Increased beta-endorphin but not met-enkephalin levels in human cerebrospinal fluid after acupuncture for recurrent pain.

Low-frequency electroacupuncture effectively alleviated recurrent pain in 10 patients. Basal levels of beta-endorphin and met-enkephalin in the lumbar cerebrospinal fluid (CSF) of these patients were not different from those in pain-free control subjects. After electroacupuncture in the patients with pain CSF beta-endorphin levels rose significantly in all subjects, but met-enkephalin levels were unchanged. These results suggest that the analgesia observed after electroacupuncture in patients with recurrent pain may be mediated by the release into the CSF of the endogenous opiate, beta-endorphin.

Acupuncture Therapy↗
PubMed1980

Regional distribution of methionine-enkephalin and substance P-like immunoreactivity in normal human brain and in Huntington's disease.

The regional distributions of substance P and Methionine-enkephalin (Met-enkephalin) were determined in normal human brains and in Huntington's disease using sensitive radioimmunoassays. Model experiments showed that both Met-enkephalin- and substance P-like immunoreactivities were stable for up to 72 h post-mortem in mouse brain. The results of high pressure liquid chromatography (HPLC) analyses indicated that the majority of the immunoreactivity detected in human globus pallidus corresponded to the native peptides, substance P or Met-enkephalin. In Huntington's disease the present results confirm that there is a substantial drop (> 80%) in the substance P content of the globus pallidus (both medial and lateral segments) and substantia nigra, and there was also a reduction (> 50%) in the Met-enkephalin content of these areas. This result suggests the loss of striato-pallidal and striato-nigral substance P and enkephalin-containing projections in Huntington's disease.

Animals↗
PubMed1980

Ectopic production of methionine enkephalin and beta-endorphin.

Immunoreactive methionine enkephalin and beta-endorphin were sought by serial dilution of tissue extracts and assay of chromatographic fractions in non-endocrine tumour tissue from three patients with the ectopic adrenocorticotrophin syndrome associated with carcinoid tumours and in normal lung tissue and thymic tissue from a patient with myasthenia gravis. In all cases serial dilution of extracts showed parellelism to standard radioimmunoassay curves. The two peptides were found in high concentration in the three tumours but were undetectable in the control tissues. In a single case tested the methionine enkephalin concentration in a vein draining the tumour was twice that in a peripheral vein. In view of their profound effect on behaviour in animals and potent analgesic activity in animals and man the ectopic secretion of methionine enkephalin and beta-endorphin may modify the clinical features of a wide variety of tumours and produce some of the diverse clinical syndromes associated with malignancy.

ACTH Syndrome, Ectopic↗
PubMed1980

Met-enkephalin circulates in human plasma.

The physiological roles of Met-enkephalin and Leu-enkephalin are still unknown. They may act as neurotransmitters in the central and peripheral nervous systems. Met-enkephalin has been detected in several species in a variety of tissues including brain, spinal cord and gut using bioassays, opiate receptor assays and radioimmunoassays (RIA). It has also been detected in human gut immunocytochemically and in human brain and cerebrospinal fluid by opiate receptor assay and RIA. However, all reported assays show some degree of cross-reaction with Leu-enkephalin and unequivocal differentiation between the two enkephalins and the larger endorphins has not always been possible. Thus the existence of Met-enkephalin in human tissues and fluids remains in doubt. Using a highly specific RIA, we have now obtained evidence that Met-enkephalin-like material circulates in the plasma of normal subjects and may be secreted by the adrenal gland. Chromatographically the material exists in plasma mainly as the intact pentapeptide and not as the biologically inactive degradation product Gly-Gly-Phe-Met as would be expected from metabolic studies.

Adrenal Glands↗