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M T Jones

Publications and source records attributed to M T Jones.

At least 91 records · Page 5Linked to original sources
PubMed1977

Structure-activity relationships of corticosteroid feedback at the hypothalamic level.

Structure-activity studies on the corticosteroid fast and delayed feedback receptor mechanisms controlling the secretion of corticotrophin releasing factor (CRF) were carried out with the rat hypothalamus in vitro. The secretion of CRF was induced by acetylcholine (3 pg/ml). The fast feedback receptor appears highly specific, and the structure essential for efficacy involves an 11beta-hydroxyl group and an unblocked 21-hydroxyl group. Several steroids showed antagonism and so the binding site is not very specific. 18-hydroxy, 11-deoxycorticosterone, progesterone, 17alpha-hydroxyprogesterone and 11-deoxycorticosterone were antagonists of fast feedback. The delayed feedback receptor required either an 11beta-or a 21-hydroxyl group for efficacy. The binding site required a 17-hydroxyl group when the 11beta- or 21-hydroxyl groups were absent. Binding also involved the 3-oxo,4,5-ene structure since steroids in which these are absent were inactive.

Acetylcholine↗
PubMed1977

cis-dichlorodiammineplatinum(II) chemotherapy in experimental murine myeloma MOPC 104E.

Data are presented indicating marked antineoplastic activity for cis-dichlorodiammineplatinum(II) in MOPC 104E myeloma. One-eighteenth of the dose that produced 100% cures can be combined with noncurative, low doses of cyclophosphamide and 1,3-bis(2-chloroethyl)-1-nitrosourea to produce antineoplastic activity of the same degree as that produced by much higher dose regimens which regularly produce cures. Since, in the past, results of therapeutic trials in plasma cell tumors in humans have paralleled results in this animal model, clinical trials of cis-dichlorodiammineplatinum in multiple myeloma appear warranted.

Animals↗
PubMed1976

The effect of dopamine on neurohypophysial hormone release in vivo and from the rat neural lobe and hypothalamus in vitro.

1. The rat hypothalamus (containing the supra-optic nuclei, paraventricular nuclei, median eminence and proximal pituitary stalk) has been incubated in vitro and shown to be capable of releasing the neurohypophysial hormones, oxytocin and arginine vasopressin, at a steady basal rate about one twentieth that of the rat neural lobe superfused in vitro. 2. The hypothalamus and neural lobe in vitro released both hormones in a similar arginine vasopressin/oxytocin ratio of about 1-2:1. However, when release was expressed relative to tissue hormone content, the hypothalamus was shown to release about three times as much arginine vasopressin and six times as much oxytocin as the neural lobe. 3. Dopamine in a concentration range of 10(-3)-10(-9)M caused graded increases in hormone release from the hypothalamus in vitro to a maximum fivefold increase over preceding basal levels. The demonstration that apomorphine also stimulated hormone release whereas noradrenaline was relatively ineffective suggested that a specific dopamine receptor was involved. A separate cholinergic component in the release process was indicated by the finding that acetylcholine stimulated release to a maximum fivefold increase in concentrations of 10(-3)-10(-9)M. 4. The fact that the isolated hypothalamus can be stimulated by dopamine and acetylcholine to release increased amount of oxytocin and arginine vasopressin raises the question of the origin and fate of the hormones released in this way. The possibility that they could be released into the hypophysial portal circulation from median eminence to affect the anterior lobe of the pituitary is discussed. 5. In similar doses, both dopamine and noradrenaline injected into the lateral cerebral ventricles of the brain of the anaesthetized, hydrated, lactating rat caused the release of arginine vasopressin and oxytocin. Apomorphine release both hormones but at a higher dose level and to less effect than the catecholamines. 6. The hormone release induced in vivo by dopamine could be prevented by the prior administration of haloperidol or phentolamine and these antagonists were equally effective in blocking the hormone release due to noradrenaline. The involvement of a specific dopamine receptor was more clearly implicated by the use of pimozide which completely inhibited the hormone release due to dopamine and apomorphine but not that due to noradrenaline. 7. It is suggested that the release of neurohypophysial hormones can be stimulated via a dopaminergic nervous pathway in addition to a cholinergic one. The possibility that the osmoreceptor mechanism for the release of antidiuretic hormone from the neural lobe of the pituitary may involve such a dopaminergic pathway is discussed.

Acetylcholine↗
PubMed1976

Effect on various putative neurotransmitters on the secretion of corticotrophin-releasing hormone from the rat hypothalamus in vitro-a model of the neurotransmitters involved.

The effect of incubating the hypothalamus of adult male rats with various neurotransmitters upon the release of corticotrophin-releasing hormone (CRH) was studied. The CRH activity in the incubation medium was assayed in 48 h median eminence-lesioned rats and the corticosteroidogenesis of excised adrenals in vitro was used as the end-point. 5-Hydroxytryptamine (100 pg/ml-10ng/ml) caused a dose-dependent release of CRH which was antagonized by methysergide (30-100 ng/ml). The response to 5-hydroxytryptamine was also inhibited by hexamethonium and atropine which indicated that it was acting through a cholinergic interneurone. Melatonin (10 ng) did not alter the basal release of CRH but inhibited the action of both 5-hydroxytryptamine (10 ng) and acetylcholine (3 pg). Thus it appears that both 5-hydroxytryptamine and melatonin play a role in the control of CRH release. Noradrenaline blocked the release of CRH induced by both acetylcholine and 5-hydroxytryptamine and presumably this inhibition was caused by direct action on the CRH neurone. gamma-Aminobutyric acid (GABA) also inhibited the release of CRH and may also be involved in the regulation of CRH secretion. The inhibitory neurotransmitters, noradrenaline, GABA and melatonin, act via independent receptor mechanisms. A model based on the above data is presented.

Acetylcholine↗
PubMed1976

Effect of bilateral adrenalectomy and corticosteroid therapy on the secretion of corticotrophin-releasing factor activity from the hypothalamus of the rat in vitro.

The rat hypothalamus in vitro preparation was used to investigate the effect of bilateral adrenalectomy, with and without replacement therapy, on the release of corticotrophin-releasing factor(CRF). Corticotrophin-releasing factor was estimated using 48 h basal hypothalamic lesioned assay rats and corticosterone production of excised adrenals was used as the end point. Bilateral adrenalectomy resulted in depletion of hypothalamic CRF content within the first 2 h after the operation but this effect was prevented by replacement therapy with corticosterone. Thereafter, the hypothalamic CRF content returned to values not significantly different from the intact control level. Bilateral adrenalectomy caused an increase in both basal and acetylcholine-induced release of CRF and it is suggested that corticosteroids exert a negative feedback effect on the hypothalamus.

Acetylcholine↗
PubMed1975

Mucociliary tracheal transport rates in man.

A new method for measuring mucociliary tracheal transport rates (MTTR's) is described. An aqueous aerosol containing albumin microspheres labeled with 99mTc was inhaled in such a manner that it was deposited in local concentrations in the large airways. These boli of microspheres were transported up the trachea and their MTTR's measured using a gamma camera. MTTR's were measured in 42 healthy nonsmoking adults (32 men and 10 women, mean age 28 yr). The mean MTTR's appeared to be log normally distributed with a geometric mean of 3.6 mm/min and a coefficient of variation of 75%. The MTTR's of men and women were similar. Each individual's short-term coefficient of variation was 25%. Twenty-two repeat studies 1 wk to 15 mo apart showed the variation within individuals was less than between individuals. The parasympatholytic drug, atropine (0.6 mg iv) decreased MTTR's for at least 3 h. Inhalation of the sympathomimetic drug, Th1165a increased MTTR's. Chronic and acute smoking did not appreciably change the MTTR'S.

Adrenergic beta-Agonists↗
PubMed1975

The effect of various putative neurotransmitters on the release of corticotrophin releasing hormone from the hypothalamus of the rat in vitro. I. The effect of acetylcholine and noradrenaline.

The effect of various putative neurotransmitters upon the release of corticotrophin releasing hormone (CRH) was investigated using the hypothalamus of the rat in vitro. Acetylcholine (1-5 pg) caused a dose-dependent release of CRH which was antagonized by hexamethonium (1-10ng) and partially antagonized by atropine (300 pg). Neither noradrenaline, dopamine nor histamine had any effect on the basal secretion of CRH. Noradrenaline (10 ng), however, was able to inhibit the release of CRH in response to acetylcholine (3 pg) and this action of noradrenaline was reduced by phentolamine (100 ng), an alpha adrenergic blocking agent.

Acetylcholine↗
PubMed1974

Stimulation electrically and by acetylcholine of the rat hypothalamus in vitro.

1. The hypophysiotrophic area of the rat hypothalamus was studied in vitro. The preparation remained viable for at least 3 hr and showed oxygen consumption varying between 68.9-120 mumole/g.hr. The tissue potassium ion content (per unit wet weight) fell to about 50% of the in vivo concentration during this time compared with 15% in the presence of ouabain (10(-4) M). Histological examination of tissue incubated for 3 hr showed variable perineuronal oedema but the nuclei were of normal appearance and none showed the pyknotic changes that would be associated with cell degeneration.2. Corticotrophin releasing hormone (CRH) in the medium pooled from five to twenty hypothalami was assayed in five to twelve rats which were median-eminence lesioned 48 hr earlier. In vitro corticosterone production of quartered adrenals was used as the end point of the assay. Regression lines of the dose-response curves for ACTH, crude CRH and different volumes of medium from electrically stimulated hypothalami were parallel. CRH output was maximal at 75 Hz and 100 muA when the square-wave pulses lasted for 1 msec. No CRH activity was found on stimulation of cerebral cortex or thalamic tissue pieces of equivalent size.3. Hypothalami taken from rats, adrenalectomized 7-14 days previously, released several-fold more CRH into the medium during electrical stimulation than the initial content of the tissue, showing that the tissue was capable of synthesizing CRH in vitro. The hypothalami taken from intact rats released considerably less CRH into the medium than tissue taken from 12 to 14 day adrenalectomized rats. The hyper-secretion of CRH observed in hypothalami taken from adrenalectomized rats was abolished by pre-treatment with 5 mg/100 g s.c. of corticosterone 24 hr before removal of the tissue. It is therefore proposed that the delayed negative feed-back action of corticosterone at the hypothalamic level is by the suppression of CRH synthesis and that the effect of secretion is secondary to the effect on synthesis.4. The presence of Ca(2+) in the medium was essential for the release of CRH.5. CRH secretion increases linearly with doses of acetylcholine from 5.5 x 10(-15)-5.5 x 10(-14) M. Cerebral cortex incubated with acetylcholine showed no CRH activity. The effect of acetylcholine was reduced by atropine (3.5 x 10(-13) M). Median eminence-pituitary stalk fragments (which contain mainly terminal axons of neurones) incubated with acetylcholine showed no CRH stimulation in the doses that activate the release of CRH using the hypophysiotrophic hypothalamus. Acetylcholine may act as a neurotransmitter at the dendritic level in the CRH neurone.

Acetylcholine↗