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Biomedical subjects

R O Morgan

Publications and source records attributed to R O Morgan.

At least 73 records · Page 4Linked to original sources
PubMed1978

A defect in thromboxane A2 synthesis may be a factor predisposing to cancer.

A failure of thromboxane (TX) A2 synthesis may be a factor in cancer. Such a loss could explain the susceptibility to mutation, the excess prostaglandin production, the glycolytic mode of metabolism and the deranged calcium pumping characteristic of cancers. Ionising radiation and phorbols both have actions similar to inhibitors of TXA2 synthesis whereas colchicine and oxygen have actions consistent with stimulation of TXA2 synthesis. The concept accounts logically for hitherto unexplained features of cancer and suggests new strategies for the prevention and treatment of cancer.

Animals↗
PubMed1978

Ultra-violet radiation and 8-methoxypsoralen have actions similar to those of known inhibitors of thromboxane A2 synthesis in rat mesenteric blood vessels.

In the rat mesenteric vascular bed three structurally different agents (imidazole, benzydamine and N-0164) which have been reported to be inhibitors of thromboxane (TX) A2 synthesis at certain concentrations, all have a characteristic spectrum of action. They inhibit pressor responses to noradrenaline and angiotensin with equal potency and the inhibition can be reversed by exogenous PGE2: they do not inhibit responses to potassium. Ultra-violet (UV) radiation has a similar spectrum of action. The main difference between the action of imidazole and that of UV radiation is that the former is rapidly reversible while the latter is not. However, irradiation administered to preparations inhibited by imidazole has no irreversible effect provided that the radiation is switched off before the imidazole is removed. The imidazole protects against radiation damage suggesting that the drug may stabilize the site affected by UV light. 8-methoxypsoralen, a light sensitizing agent used in treatment of psoriasis also inhibited noradrenaline and angiotensin but not potassium responses and seemed to make the preparation more sensitive to radiation damage. It is possible that UV radiation and 8-methoxypsoralen may inhibit TXA2 synthesis but this requires confirmation by direct methods.

Angiotensin II↗
PubMed1978

Influence of agents which modulate thromboxane A2 synthesis or action on R3230AC mammary carcinoma.

The effects of agents which modulate thromboxane A2 synthesis or action, were tested in the R3230AC transplanted mammary tumour. Three different inhibitors of thromboxane A2 synthesis or action (copper, dipyridamole and diazepam) all caused an increase in tumour growth. Colchicine and melatonin, both stimulators of thromboxane A2 synthesis, inhibited the growth of the tumour significantly.

Animals↗
PubMed1978

Prostaglandins and schizophrenia: further discussion of the evidence.

It has been proposed that schizophrenia is a prostaglandin-deficiency disease and also that it is a disease of prostaglandin excess. New evidence is reviewed which suggests that 'classic' schizophrenia is due to a specific deficiency of prostaglandin E1 while certain toxic and vitamin-deficiency psychoses may be due to a broader spectrum of prostaglandin deficiency. There is also good evidence that a particular schizophrenic subgroup, which includes catatonic schizophrenia but may not be confirmed to it, is associated with an excess of prostaglandins. Part of the explanation may be that prostaglandin E1 has a 'bell-shaped' dose-response curve with high concentrations having effects similar to those of prostaglandin deficiency.

Animals↗
PubMed1978

Dantrolene blocks intracellular calcium release in smooth muscle: competitive antagonism of thromboxane A2.

Dantrolene sodium has been shown to block the release of intracellular calcium in skeletal muscle. It has been proposed that dantrolene blocks the movement and (or) action of a natural calcium ionophore. In a rat vascular preparation dantrolene was found to inhibit pressor responses to noradrenaline and angiotensin but not those to potassium with an IC50 concentration within the therapeutic levels in man. Imidazole, an inhibitor of thromboxane A2 (TXA2) synthesis, had similar actions to dantrolene. Interactions between imidazole and dantrolene suggested that dantrolene may be a competitive antagonist of TXA2 in muscle. We report the first demonstration of an effect of dantrolene sodium on smooth muscle contractility and suggest that TXA2 is an essential modulator of vascular reactivity. A similar role has been shown for TXA2 in platelets.

Angiotensin II↗
PubMed1978

Regulation of cytoplasmic calcium: interactions between prostaglandins, prostacyclin, thromboxane A2, zinc, copper and taurine.

The regulation of cytoplasmic calcium is a key process in nerve tissue. Using a smooth muscle model we have shown that prostaglandin (PG) E2 probably regulates entry from extracellular fluid, whereas the release from intracellular stores depends on the interplay between thromboxane (TX) A2, PGEI and prostacyclin. Hormones and other agents interact with this system in the following ways: vasopressin, angiotensin and inositol mobilize arachidonic acid from membrane phospholipids and increase synthesis of PGE2 and TXA2, cortisol blocks this action. Prolactin and zinc mobilize dihomo-gamma-linolenic acid and increase synthesis of PGEI. These effects can be blocked by cortisol, lithium and taurine, three agents which on their own have no effect on basal PG production. Epileptogenic agents like penicillin and picrotoxin also stimulate PG synthesis, while diphenylhydantoin is a PG antagonist and diazepam is a TXA2 antagonist. The effects of all these agents occur at concentrations which are physiological in the case of the natural ones, and readily attained in human plasma in the case of the drgus. In view of recent evidence that calcium may be important in demyelination and considering the established role it plays in nerve conduction and synaptic transmission, we suggest that these observations may be of significance in understanding Friedreich's ataxia.

Animals↗
PubMed1978

Adenosine as a prostaglandin antagonist. Possible mechanism of the defect in combined immunodeficiency disease due to adenosine deaminase deficiency.

Adenosine inhibition of cell division in EB-virus-transformed human lymphocytes and in normal lymphocytes stimulated by phytohemagglutinin can be overcome by prostaglandin (PG) E2. Analysis of adenosine/PGE2 interactions in smooth muscle suggests that adenosine causes immuno-deficiency by blocking a PG-dependent calcium stage of lymphocyte activation.

Adenosine↗
PubMed1977

Adenosine as a natural prostaglandin antagonist in vascular smooth muscle.

Adenosine has actions on smooth muscle similar to those of prostaglandin (PG) antagonists. Like some PG antagonists it is a phosphodiesterase inhibitor and seems to interfere with calcium effects. It has agonist/antagonist interactions with theophylline, a PG antagonist. In rat mesenteric vascular smooth muscle adenosine blocked responses to noradrenaline which depend on release of intracellular calcium but not those to potassium ions which depend on calcium entry from extracellular fluid. Partial inhibition of endogenous PG synthesis by indomethacin enhanced the adenosine effect. In preparations in which vascular reactivity had been abolished by indomethacin and then partly restored by 1 or 5 ng/ml PG2, adenosine also inhibited responses to noradrenaline: the curve for the 5 ng/ml PG2 concentration was to the right of and parallel to the 1 ng/ml curve consistent with a competitive interaction between adenosine and PG2. Similar interactions between adenosine and PG2 were shown in human lymphocytes in which activation also depends on calcium release. These findings suggest how calcium-dependent metabolic responses may be controlled and indicate further reasons for caution in the interpretation of cyclic AMP experiments.

Adenosine↗
PubMed1977

Effects of propranolol on the responses of the rat stomach strip to prostaglandin E2.

Propranolol is a local anaesthetic, membrane-stabilizing drug as well as a beta blocker. 2 mug/ml is added to many PG bioassay systems in order to inhibit beta adrenergic effects. This concentration inhibited responses of the rat stomach strip to PGE2 concentrations below 5 x 10(-7)M but potentiated responses to higher PGE2 concentrations. In calcium-free buffer only the potentiation was seen. Propranolol may not be a suitable drug for use in PG bioassay systems.

Animals↗
PubMed1977

Myo-inositol in physiological concentrations stimulates production of prostaglandin-like material.

In physiological concentrations myo-inositol stimulated production of prostaglandin (PG)-like material in a rat mesenteric vascular bed preparation. There were five lines of evidence: 1. Inositol potentiated pressor responses to both norepinephrine and potassium in a manner similar to PGE2. 2. Inositol had no potentiating effect in preparations in which endogenous PG production was blocked by indomethacin. 3. Inositol caused no further potentiation in preparations already potentiated by arachidonic acid, the PG precursor. 4. The inhibitory effect of the PG antagonist chloroquine was reduced in an apparently competitive manner by inositol. 5. As indicated by rat stomach bioassay inositol caused a three fold rise in the outflow of PG-like material from the preparation.

Animals↗