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Biomedical subjects

D E Clarke

Publications and source records attributed to D E Clarke.

At least 109 records · Page 6Linked to original sources
PubMed1979

Rat and human cardiac monoamine oxidase: a comparison with other tissues.

Experiments were made to test the proposal that rat heart mitochondrial monoamine oxidase (MAO) differs from that in certain other organs. Using kynuramine as the substrate, cardiac MAO of rats was compared with that in the vas deferens and liver. While the relative proportions of type A and B MAO varied between the three tissues, the sensitivity of the MAO types to preferential inhibitors, mixed substrate interactions and apparent Km determinations failed to reveal differences. Human atria contained mostly type B MAO, but the properties of the A and B types were not radically different from those found in rat tissues. No clorgyline-resistant MAO activity was detected with kynuramine, either in the rat or human tissues. Differences in rat heart MAO seem to be exposed by some substrates but not others, such as kynuramine.

Aging↗
PubMed1979

The reaction of rabbit muscle creatine kinase with diethyl pyrocarbonate.

The reaction of rabbit muscle creatine kinase with diethyl pyrocarbonate was studied. It was found that up to five of the sixteen histidine groups per enzyme subunit could be modified, and under the conditions employed, there was no evidence for formation of the disubstituted derivative of histidine. Evidence was obtained for small but significant amounts of modification of lysine and cysteine groups; tyrosine groups were not modified. Modification of the enzyme led to inactivation; this could be protected against by inclusion of substrates or, more effectively, by inclusion of the combination MgADP plus creatine plus nitrate, which is thought to produce a 'transition-stage-analogue' complex. Analysis of data on the rates of inactivation and the stoicheiometry of modification suggested that there was one essential histidine group per enzyme subunit, modification of which led to inactivation.

Adenosine Diphosphate↗
PubMed1978

Rectal absorption of homatropine [14C]methylbromide in the rat.

Homatropine[14C]methylbromide (HMB-14C) was administered to rats by intramuscular injection, oral gavage and rectal suppository. Plasma concentration of 14C were measured over the subsequent 12 h. Peak plasma concentrations were higher and achieved more rapidly after rectal administration than by the other routes whether HMB-14C was administered in a water-soluble suppository base or in aqueous solution. Twelve h after the suppositories were inserted and retained 28% of the 14C had been excreted in the urine while 56% remained in the large intestine. Unlabelled HMB, given in rectal suppositories to anaesthetized rats, caused prompt blockade of the effects of vagal stimulation on pulse rate and of intravenous acetylcholine on blood pressure. These results confirm the rapid rectal absorption of the drug.

Absorption↗
PubMed1977

Observations on the monamine oxidase activity of rat vasa deferentia, major blood vessels and human saphenous vein.

Monoamine oxidase (MAO) activity was characterized using whole tissue homogenates and kynuramine as the substrate. In rat vasa deferentia, kynuramine deamination was differentially inhibited by clorgyline, less so by deprenyl and not at all by pargyline. These studies, and mixed substrate experiments with tryptamine, proved that kynuramine is a substrate for MAO types A and B. Experiments made with rat abdominal aorta and inferior vena cava disclosed clorgyline-sensitive and resistant MAO activity, the latter being inhibited by semicarbazide but not by deprenyl or pargyline. No semicarbazide-sensitive species of MAO was found in human saphenous vein which also differed from the rat vasculature in that the predominant MAO activity was of the B type. It is concluded that kynuramine is also a good substrate for clorgyline-resistant enzymes and that rat vasculature may be a poor model for predicting deaminating mechanisms in human venous tissue.

Adult↗
PubMed1977

Acute and chronic effects of tetrahydrocannabinols on monoamide oxidase activity: possible vehicle/tetrahydrocannabinol interactions.

The acute and chronic effects of delta9 and delta8-tetrahydrocannabinol (THC) were studied on the monoamine oxidase (MAO) acitvity of various organs of the rat. The experimental design included two vehicles for the cannabinols (1% Tween 80 in saline and ethanol) and a further control group, given saline only. Neither delta9 nor delta8-THC (1 and 14 mg/kg, i.p.) altered MAO activity after one day and no changes from the saline control were found in the vehicle-treated groups. However, drug (delta8 and delta9-THC 1 mg/kg, i.p.) and vehicle-induced changes were observed after 14 days (Tween 80) and 28 days (ethanol) of continuous daily treatment. These data were interpreted upon the basis of a possible time-dependent, vehicle/drug interaction at the level of outer mitochondrial membranes. Contrary to previously published reports, no compelling evidence was obtained for any inherent pharmacological effect of the cannabinols upon MAO activity.

Animals↗
PubMed1976

Neurogenic influences of bilateral adrenalectomy on monoamine oxidase.

Bilateral adrenalectomy (10 days) increased the monoamine oxidase activity of the rat heart, vas deferens, spleen, superior cervical ganglion, and hypothalamus but not that of the rest of the brain, kidney, and liver. Experiments were made to determine whether the increased activity was due to neurogenic influences and whether the enhanced activity of monoamine oxidase was intra- or extraneuronally located. Ganglionic blockade with chlorisondamine failed to alter the rise in cardiac monoamine oxidase. Likewise, superior cervical ganglion monoamine oxidase was unaffected by surgical denervation. 6-Hydroxydopamine abolished the increase in monoamine oxidase activity of the vas deferens, spleen, and superior cervical ganglion but failed to alter that of the kidney, hypothalamus, and the rest of the brain. Cardiac monoamine oxidase was reduced markedly by 6-hydroxydopamine, but the remaining activity was still significantly elevated over the respective control values. The data suggest that the increase in organ monoamine oxidase is predominantly of neuronal origin and that this increase is not due to transsynaptic induction.

Adrenal Glands↗
PubMed1976

Studies on the biochemical aspects of the 'disulfiram-like' reaction induced by oral hypoglycemics.

In vitro experiments, using rat liver homogenates, were designed to examine certain of the proposed enzymatic mechanisms for the interaction of oral hypoglycemic drugs with monoamine and ethanol metabolism. The oxidative degradation of tryptamine was studied by measuring indoleacetic acid (IAA) production and conclusions were drawn with regard to the activity of monoamine oxidase, aldehyde dehydrogenase and ethanol dehydrogenase. Acetohexamide, hydroxyhexamide, tolazamide, tolbutamide and chlorpropamide failed to reveal any specific inhibition of the three enzymes. Ethanol (0.2% w/v) and disulfiram decreased IAA formation, as did a lack of available aldehyde dehydrogenase and NAD, but these reductions were not enhanced by the hypoglycemic agents. The results suggest that the 'disulfiram-like' reaction which occurs in certain patients imbibing ethanol while receiving oral hypoglycemic drugs, depends upon some factor(s) other than, or additional to, a specific interference with monoamine and/or ethanol metabolism.

Administration, Oral↗
PubMed1976

Blood pressure responses to adrenal field stimulation as a measure of adrenal catecholamine release.

1 A new method for studying adrenal medullary release is described in pithed rats using field stimulation of an entire adrenal gland. 2 The increases in blood pressure in response to field stimulation of the gland consisted of an initial short, variable component, due to stimulation of adrenergic vasomotor neurones and a secondary, longer lasting component, due to medullary catecholamine release. 3 Removal of the initial component by drugs or cardiac/coeliac ganglionectomy did not affect the magnitude of the secondary pressor component. 4 The secondary pressor component was frequency-dependent, reproducible and stable with time. The extent of medullary catecholamine release could be assessed by comparing the blood pressure rise with those obtained after adrenaline injections. 5 The method appears to provide a reliable means by which adrenal medullary catecholamine release may be assessed without significant interference from vasomotor nerves.

Adrenal Glands↗
PubMed1975

L-Thyroxine and monoamine oxidase activity in the kidney and some other organs of the rat.

L-Thyroxine (T4) (10,30 and 300 mug/kg. S.C. for 5 days) increased kidney monoamine oxidase (MAO) activity and decreased that of the liver, using tryptamine as the substrate. These changes were dose-dependent. Time-dependent changes were found with the 30 mug/kg dose. Heart MAO activity was increased by the high dose while small decreases were found with the lower doses. No changes were found in the whole brain, vasa deferentia, the thyroid or adrenal glands. Hypophysectomized rats showed a 50% reduction in kidney MAO which was fully restored following T4 (10 mug/kg/day) treatment. Evidence was obtained that both T4 and L-triiodothyronine can activate the deaminating activity of MAO in vitro. Thus, T4 and/or its metabolites may play a physiological role in the maintenance of kidney MAO activity. The mechanism(s) whereby T4 and/or its metabolites alter kidney MAO activity is not resolved but direct effects upon the various forms of MAO and/or influences upon regulating substances seems likely to be involved.

Animals↗