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Biomedical subjects

D F Horrobin

Publications and source records attributed to D F Horrobin.

At least 271 records · Page 15Linked to original sources
PubMed1980

Prolactin as a regulator of fluid and electrolyte metabolism in mammals.

The evidence that prolactin is a fluid and electrolyte regulator in mammals is reviewed, with particular emphasis on the renal actions of prolactin. Prolactin receptors are found in mammalian kidneys. Prolactin modulates renal formation of cyclic AMP and polyamines and it leads to demonstrable histological changes in the proximal tubules. The renal actions of prolactin primarily involve modulation of the effects of other hormones and are therefore critically dependent on the background physiological situation. Prolactin seems able to cause a prolonged reduction in water, sodium, and potassium excretion, a pattern that is imitated by no other hormone with the possible exception of growth hormone. Prolactin preparations can cause an acute antidiuresis, which may in part be related to contamination of prolactin preparations with vasopressin. However, most of the described effects cannot be explained by vasopressin contamination. This is particularly so with the effects of prolactin on water movements across fetal skin, the amniotic membrane, and in the eye where prolactin and vasopressin have diametrically opposite effects. It is concluded that prolactin is a regulator of fluid and electrolyte metabolism in mammals but that it is a modulator rather than a primary controlling factor.

Aldosterone↗
PubMed1980

Schizophrenia: a biochemical disorder?

There is evidence that schizophrenia may be related to excess biological activity of dopamine, deficient synthesis of a prostaglandin and to the presence of a normal opioid in excess or of an abnormal opioid. These three groups of observations seem to be interrelated since opioids are able to inhibit the formation of prostaglandin E1 and prostaglandin E1 and dopamine inhibit each other's effects. A low prostaglandin E1 level will therefore produce and apparent dopamine excess. Niacin causes flushing, apparently by stimulating production of prostaglandin E1. Much larger doses of oral niacin are required to produce flushing in schizophrenics than in normal individuals. Most schizophrenics do not flush when given 250 mg orally and this may be a simple biochemically-based test for a major group of schizophrenics.

Animals↗
PubMed1979

Mind and cancer.

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Animals↗
PubMed1979

Schizophrenia: Reconciliation of the dopamine, prostaglandin, and opioid concepts and the role of the pineal.

In recent years it has been suggested that the biological defect in schizophrenia may be related to excess dopamine activity, to production of an abnormal opioid or a normal opioid in excess, to a prostaglandin deficiency, to a hypersensitivity to wheat proteins, to an allergic phenomenon, to a defect in zinc metabolism, or to a pineal deficiency. The present hypothesis proposes that the various concepts are not mutually exclusive but represent different aspects of the same problem. The final common path in schizophrenia may be a failure of formation and action of prostaglandins of the 1 series.

Allergens↗
PubMed1979

Progesterone interferes with the actions of prostaglandin (PG) E1 but not those of PGE2 or PGF2 alpha in a rat vascular preparation.

In the mammary gland some actions of prolactin seem mediated by PGs. Progesterone blocks several of the mammary effects of prolactin. We therefore investigated the effects of 100 ng/ml progesterone (within the normal human plasma concentration in pregnancy) on the vascular effects of PGE2, PGEF2 alpha and PGE1. Progesterone had no effects on the responses to PGE2 and PGF2 alpha but significantly (p less than 0.01) attenuated the actions of low concentrations of PGE1. It may have enhanced the actions of high PGE1 concentrations. Progesterone appears able to block some effects of PGE1 and to imitate others.

Animals↗
PubMed1979

Differential regulation of the formation of prostaglandins and related substances from arachidonic acid and from dihomogammalinolenic acid. I. Effects of ethanol.

Ethanol, over the concentration range 33 to 300 mg/100 ml (7.2-65.2 x 10-3 M) caused a dose dependent and highly significant enhancement of conversion of 14C-dihomogammalinolenic acid (DGLA) to prostaglandin (PG) El and to thromboxane (Tx) B1 by human platelets. Ethanol had no significant effect on conversion of 14C-arachidonic acid to PGE2 and TxB2. This concentration range is the one involved in human alcoholic intoxication. The effect could be related to enhanced transport of DGLA to the active site of the cyclo-oxygenase enzyme complex, to a modification of the enzyme complex which changes the way it metabolizes DGLA but not arachidonic acid or to two different enzymes. Whatever the mechanism it seems that it is possible to regulate selectively the formation of 1 and 2 series PGs probably at the cyclo-oxygenase level. The physiological and clinical implications of this are discussed.

8,11,14-Eicosatrienoic Acid↗
PubMed1979

Differential regulation of the formation of prostaglandins and related substances from arachidonic acid and from dihomogammalinolenic acid. II. Effects of vitamin C.

Vitamin C over the concentration range 10 to 100 microgram/ml (5.7-57 x 10-5 M) caused a dose dependent and highly significant enhancement of conversion of 14C-dihomogammalinolenic acid (DGLA) to prostaglandin (PG) E1 and to thromboxane (Tx) B1 by human platelets. Vitamin C had no effect on conversion of 14C-arachidonic acid to PGE2 and TxB2. The concentration range is relevant to physiology: in some cells which concentrate the vitamin, such as polymorphonbuclear leucocytes and the adrenal cortex, vitamin C concentrations may be substantially higher than 100 microgram/ml. Vitamin C can therefore selectively enhance the formation of cyclo-oxygenase generated products from DGLA without changing formation of those from AA. This effect can account for a number of the known actions of vitamin C including its effect on the immune system. The implications of this finding are discussed.

8,11,14-Eicosatrienoic Acid↗
PubMed1979

Multiple sclerosis: the rational basis for treatment with colchicine and evening primrose oil.

Multiple sclerosis (MS) is a disease with no known treatment. In view of this and of its distressing nature patients are attracted by any new concepts. As a reaction to this neurologists are sometimes excessively sceptical and fail to consider new approaches seriously. Recent attempts have been made to treat multiple sclerosis with polyunsaturated fatty acids and with colchicine. This approach is not arbitrary and is firmly grounded in fundamental basic scientific concepts. In patients with multiple sclerosis there is evidence of both an abnormality in essential fatty acid metabolism and an abnormality in lymphocyte function. It is now apparent that the fatty acid abnormality may cause the lymphocyte abnormality and that both may be improved by dietary manipulation. There is also evidence that the demyelination may be associated with recurrent inflammatory episodes and with entry of calcium into the cytoplasm. In vitro colchicine has been shown to have actions compatible with regulation of cytoplasmic calcium and in two diseases characterised by intermittent inflammatory episodes (Behçets syndrome and familial Mediterranean fever) it has been found to prevent or to reduce the severity of such episodes. Preliminary results suggest that combined therapy with evening primrose oil and colchicine may be of considerable value.

Behcet Syndrome↗
PubMed1979

The nutritional regulation of T lymphocyte function.

Prostaglandin (PG) E1 plays a major role in the regulation of thymus development and T lymphocyte function and the evidence for this is reviewed. The production of PGE1 is dependent on nutritional factors with linoleic acid, gamma-linolenic acid, pyridoxine, zinc and vitamin C playing key roles. Inadequate intake of any one of these will lead to inadequate PGE1 formation and defective T lymphocyte function. Megadoses of any one are likely to be only minimally effective in the absence of adequate intakes of the others. By careful attention to diet it should be possible to activate T lymphocyte function in the large number of diseases including rheumatoid arthritis, various auto-immune diseases, multiple sclerosis, and cancer in which such function is defective. It is possible that T lymphocytes may require both endogenous and exogenous PGE1 in order to function adequately. It is therefore of particular interest that many cancer cells and virally infected cells are unable to make PGE1 because they cannot convert linoleic acid to gamma-linolenic acid. The direct provision of gamma-linolenic or dihomo-gammalinolenic acids in these situations is worthy of full investigation.

Animals↗
PubMed1979

The regulation of prostaglandin E1 formation: a candidate for one of the fundamental mechanisms involved in the actions of vitamin C.

Vitamin C stimulates the formation of PGE1 in human platelets. The effect occurs over the physiologically relevant range of concentrations. PGE1 is required for T lymphocyte function and plays a major part in the regulation of immune responses. PGE1 is also important in the regulation of collagen and ground substance metabolism, in cholesterol metabolism and in regulation of responsiveness to insulin. It is proposed that defective formation of PGE1 could account for many of the features of scurvy and for many of the reported therapeutic effects of vitamin C. If correct, vitamin C will be of value only in conjunction with an adequate supply of dihomogammalinolenic acid, the precursor of PGE1. Essential fatty acids, pyridoxine and zinc are all required to achieve this.

Animals↗