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Biomedical subjects

S E Gartside

Publications and source records attributed to S E Gartside.

25 records · Page 2Linked to original sources

Mediation of ACTH and prolactin responses to 5-HTP by 5-HT2 receptors.

Serotonin has a facilitatory role in the role of prolactin and adrenocorticotropin (ACTH) secretion. The serotonin precursor 5-hydroxy-L-tryptophan (5-HTP) dose dependently (30-100 mg/kg i.p.) increased plasma prolactin and ACTH in the male rat. Prolactin and ACTH responses to 5-HTP (100 mg/kg) were attenuated by pretreatment with the non-selective 5-HT receptor antagonist, metergoline (0.5 mg/kg), and by the selective 5-HT2 receptor antagonists, ritanserin (0.4 mg/kg), ketanserin (2.5 mg/kg), ICI (5.0 mg/kg) and spiperone (1.0 mg/kg). The 5-HT1 receptor antagonists, propranolol (40 mg/kg) and pindolol (4.0 mg/kg), failed to antagonize the prolactin and ACTH responses to 5-HTP (100 mg/kg), as did the selective 5-HT3 receptor antagonist, BRL 43694 (1.0 mg/kg). The results suggest that the prolactin and ACTH responses to 5-HTP in the male rat are mediated by 5-HT2 receptors.

5-Hydroxytryptophan↗

Endocrinological responses to 5-HT.

There is increasing evidence that neuroendocrine and temperature responses in humans can be employed to study the functional sensitivity of different 5-HT receptor subtypes. The evidence suggests that the PRL response to LTP is mediated by 5-HT1 receptors, perhaps the 5-HT1A subtype, though further studies are needed to confirm this effect. It is uncertain whether the PRL responses to other 'presynaptic' challenges of 5-HT function, for example, fenfluramine, are mediated by the same post-synaptic 5-HT receptor subtype as that for LTP. Conversely it seems likely that agonists which stimulate 5-HT2/1C receptors increase both plasma PRL and ACTH in humans. There is also evidence that 5-HT1A receptors can increase ACTH secretion. This suggests that in humans as in animals both the 5-HT1A and 5HT2/1C receptors can facilitate ACTH release, though the significance of this dual control is not understood. It is also possible that both 5-HT1A and 5-HT2/1C receptors stimulate PRL release, but 5-HT1A receptors may have a more prominent role in GH secretion. In both human and animal studies 5-HT1A and 5-HT2 receptor agonists may produce opposite effects on body temperature. These recent developments in 5-HT neuroendocrinology have been of great interest, but much is still uncertain. Progress in this field will be considerably advanced by the availability of new selective 5-HT receptor ligands, particularly selective receptor antagonists.

Animals↗

Effect of moderate weight loss on prolactin secretion in normal female volunteers.

Sleep-related prolactin secretion and prolactin responses to the infusion of low doses of the dopamine antagonist, metoclopramide, and thyrotropin-releasing hormone were measured in 11 female volunteers before and after undertaking a diet in which they lost a mean of 3.1 kg in weight in 3 weeks. No effect of weight loss on these measures was found, but there was a significant, although modest, reduction in fasting plasma tryptophan concentration without any change in the concentration of competing amino acids.

Adult↗

The effect of moderate weight loss on overnight growth hormone and cortisol secretion in healthy female volunteers.

The effects of moderate weight loss on overnight growth hormone and cortisol secretion were determined in 11 healthy women volunteers who lost an average of 3.1 kg in weight after undertaking a 1000-kcal diet for 3 weeks. There was a reduction in sleep-related growth hormone secretion and an increase in the value of the nocturnal cortisol nadir although mean overnight cortisol secretion was not significantly altered. Moderate weight loss may contribute towards some of the endocrine abnormalities seen in depressed patients.

Adult↗

Acute effects of 3,4-methylenedioxymethamphetamine (MDMA) on 5-HT cell firing and release: comparison between dorsal and median raphe 5-HT systems.

It is proposed that 3,4-methylenedioxymethamphetamine (MDMA; Ecstasy) is more toxic to 5-HT neurones projecting from the dorsal raphe nucleus (DRN) than to those from the median raphe nucleus (MRN). Since increased 5-HT release has been associated with MDMA-induced neurotoxicity, MDMA may have a DRN-selective 5-HT releasing effect. Here we have compared the effects of acute MDMA on DRN and MRN 5-HT pathways using in vivo electrophysiological and neurochemical techniques. MDMA inhibited the firing of 5-HT neurones in both the DRN and the MRN, and did so with similar potency (ED50 values, 0.589 +/- 0.151 (8) and 0.588 +/- 0.207 (6) mg/kg i.v., respectively). In both nuclei this inhibitory effect was reversed by the selective 5-HT1A receptor antagonist, WAY 100635 (0.1 mg/kg i.v.). Microdialysis measurements were made in the frontal cortex and dorsal hippocampus, regions which receive a DRN- and an MRN-selective 5-HT innervation, respectively. A dose of 1 mg/kg i.v. MDMA increased extracellular 5-HT 3-fold in both the frontal cortex and dorsal hippocampus. A higher dose (3 mg/kg i.v.) increased 5-HT levels 8-fold in both regions. Overall, our data suggest that MDMA releases 5-HT from the cell body and terminal regions of both DRN and MRN 5-HT pathways, and does so in a qualitatively and quantitatively similar fashion. We conclude that any DRN-selectivity in the neurotoxic effects of MDMA is not due to a DRN-selective, acute 5-HT releasing action of the drug.

Chromatography, High Pressure Liquid↗