Search PubMed⌕ Search

Biomedical subjects

S A Hunter

Publications and source records attributed to S A Hunter.

At least 37 records · Page 2Linked to original sources
PubMed1985

Prostaglandins and cannabis XIV. Tolerance to the stimulatory actions of cannabinoids on arachidonate metabolism.

The stimulation of prostaglandin E2 synthesis by delta 1-tetrahydrocannabinol in cultured cells is rapidly diminished by successive exposures to the drug at 24-hr intervals. Cannabidiol and cannabicyclol, two other constituents of cannabis, also displayed this in vitro tolerance effect. The phenomenon could, in addition, be observed by measuring the release of arachidonic acid from these cells, suggesting that the site of action of the cannabinoids is at one or more of the lipases that are believed to control prostaglandin synthesis under most conditions. Tolerance to cannabinoid action has been reported for a variety of in vivo parameters; thus, this in vitro system exhibits similar behavior and may, therefore, be a good model for studies on the molecular mechanisms involved in tetrahydrocannabinol action.

Arachidonic Acid↗
PubMed1984

Prostaglandins and cannabis--XIII. Cannabinoid-induced elevation of lipoxygenase products in mouse peritoneal macrophages.

The phospholipases controlling the release of arachidonic acid in mouse peritoneal macrophages have been shown to be stimulated by the natural psychoactive cannabinoids. A close correlation was observed between the potencies of these substances in elevating arachidonate levels in vitro and the reported activities in a behavioral assay in monkeys and in producing a "high" in humans. The order of activity with the macrophages was delta 1-tetrahydrocannabinol (delta 1-THC) greater than 7-OH-delta 1-THC greater than 6 alpha-OH-delta 1-THC greater than 6 beta-delta 1-THC much greater than delta 6-THC-7-oic acid. It is suggested that this effect, which has now been shown in several diverse cell types, may serve as a model for studying the mechanism of action of THC.

Animals↗
PubMed1984

Stimulation of sphingomyelin hydrolysis by cannabidiol in fibroblasts from a Niemann-Pick patient.

The hydrolysis of sphingomyelin in cells derived from a Niemann-Pick patient was studied using both a labelled precursor and measurement of endogenous levels. In vitro exposure of the cells to cannabidiol resulted in a large decrease in both the relative and absolute amounts of this lipid; the drug had a smaller effect on normal fibroblasts. Cannabidiol has been tested in the clinic as an antiepileptic agent with some success; our findings suggest that it may also be useful in relieving the symptoms associated with Niemann-Pick disease.

Cannabidiol↗
PubMed1984

Stimulation of prostaglandin synthesis in WI-38 human lung fibroblasts following inhibition of phospholipid acylation by p-hydroxymercuribenzoate.

The release of arachidonic acid and its metabolites, prostaglandin E2 and thromboxane A2, from WI-38 human lung fibroblasts was modulated by p-hydroxymercuribenzoate. Exposure to the inhibitor resulted in a dose-dependent decrease in [1-14C]arachidonic acid uptake and incorporation into phospholipids and neutral lipid pools. Activities of lung fibroblast arachidonyl-CoA synthetase and lysolecithin acyltransferase were inhibited by 100 microM p-hydroxymercuribenzoate. [14C]Arachidonic acid labelled fibroblasts exhibited an increased release of [14C]arachidonate and [14C]prostaglandin E2 of 54% and 112%, respectively, when exposed to 100 microM of inhibitor. The stimulatory effects of 8.0 microM delta 1-tetrahydrocannabinol on arachidonate release and prostaglandin E synthesis (Burstein, S., Hunter, S.A., Sedor, C. and Shulman, S. (1982) Biochem. Pharmacol. 31, 2361-2365) were modified by the inclusion of inhibiting agent, resulting in a 608% stimulation in arachidonic acid release, while prostaglandin E2 and thromboxane A2 synthesis increased 894% and 390%, respectively, over levels obtained by untreated cells. The levels of arachidonate metabolites were altered by inhibitor when compared to cells treated with cannabinoid alone. No significant inhibition by delta 1-tetrahydrocannabinol was found on arachidonic uptake in these cells. In unlabelled studies, p-hydroxymercuribenzoate resulted in a profound, dose-dependent stimulation of prostaglandin E synthesis of 1490% at 150 microM inhibitor concentration. These results provide evidence that free arachidonate is reincorporated via acylation, thereby implicating this pathway as a possible control mechanism for the synthesis of arachidonic acid metabolites.

1-Acylglycerophosphocholine O-Acyltransferase↗
PubMed1983

An evaluation of the side effects of garlic as an antihypertensive agent.

Eight spontaneously hypertensive rats representative of a diverse group with regard to age and sex were used to observe possible side effects from the use of garlic as an antihypertensive agent. Doses were administered at 6 h intervals daily for 28 days. Blood pressure, pulse rate and ECG were monitored once every 7 days for 28 days and then again 6 days after the day that the last dose was administered. All of the animals had erratic pulse rates and abnormal ECG. Weight loss occurred in all of the animals receiving the extract two and three times a day. All of the animals tested became lethargic and weak, had soft faeces and showed signs of dehydration. Also, the skin on the hindlimbs and forelimbs became very tender and could be easily torn. These effects were more pronounced in the animals receiving the extract two and three times a day.

Animals↗
PubMed1983

Prostaglandins and cannabis. XII. The effect of cannabinoid structure on the synthesis of prostaglandins by human lung fibroblasts.

Earlier findings indicated that several other cannabinoids in addition to delta 1-tetrahydro-cannabinol (THC) were able to stimulate the synthesis of prostaglandins in cell culture systems. The present study was initiated to delineate the structural requirements for this effect within the cannabinoid series. Among the primary cannabinoids, we found that the trend was for more planar structures to show greater activity. In the case of THC metabolites, the order of activity was delta 1-THC greater than 7-oxo-delta 1, 6-THC greater than 7-OH-delta 1-THC greater than 3"-OH-delta 1-THC = 6 beta-OH-delta 1-THC = 6 alpha-OH-delta 1-THC greater than delta 1, 6-THC-7-oic acid. The latter sequence compares favorably with the available data on the behavioral assay in the rhesus monkey and the subjective "high" in humans. We also observed a good correlation between the release of arachidonic acid and the production of prostaglandin E, over a series of eight cannabinoids. This gives further support that the site of action in this effect is the elevation of activity of the phospholipase(s) responsible for supplying precursor arachidonic acid for prostaglandin synthesis.

Arachidonic Acids↗
PubMed1982

Prostaglandins and cannabis--IX. Stimulation of prostaglandin E2 synthesis in human lung fibroblasts by delta 1-tetrahydrocannabinol.

Preliminary data [S. Burstein and S. A. Hunter, Biochem. Pharmac. 27, 1275 (1978)] showed that cannabinoids at levels of 1 microM or greater elevated the concentrations of prostaglandins in cell culture models. Further study [S. Burstein and S. A. Hunter, J. clin. Pharmac. 21, 240S (1981)] led to the suggestion that this effect was due to a stimulation of phospholipase A2 resulting in the release of free arachidonic acid which was then partly converted into the prostaglandin(s) normally synthesized by the particular target system. The present report gives detailed data on the cannabinoid-induced synthesis of prostaglandin E2 by te WI-38 fibroblast derived from human lung. The effect could be blocked by pretreatment with mepacrine, a phospholipase inhibitor, and aspirin, a cyclooxygenase inhibitor. These findings lend support to the hypothesis that some of the in vivo actions of the cannabinoids are due to modulations in prostaglandin synthesis at various tissue sites.

Arachidonic Acid↗
PubMed1982

Prostacyclin production by vein grafts in the arterial circulation: a study in rats.

The in vitro production of prostacyclin by vein grafts was measured using vascular rings followed by radioimmunoassay of the medium. The grafts were prepared by interposing a segment of epigastric vein in a gap in the ipsilateral femoral artery of the rat. Measurements made over a period of 1 to 42 days showed a progressive rise from venous levels (less than 0.2 ng/ml) to values close to the arterial controls (10.9 +/- 2.2 ng/ml). This deficiency of prostacyclin synthesis during the "arterialization" of the graft may account for some of the early failures which can occur in vein grafting and suggests the possibility of pharmacological intervention to improve the success rate.

Animals↗
PubMed1980

The nature of the inhibition of cholesterol esterase by delta 1-tetrahydrocannabinol.

An improved assay for cholesterol esterase based on the use of fatty acid radiolabelled cholesterol esters has been developed. The method was used to demonstrate the effects of delta 1-tetrahydrocannabinol on a crude Leydig cell esterase preparation and on crystalline pancreatic esterase. Both enzymes were inhibited and the Km values determined (6.6 mumol/1 for the Leydig cell esterase and 6.25 mumol/1 for the pancreatic enzyme). While the former exhibited a mixed type of inhibition, the latter clearly was competitive.

Animals↗
PubMed1980

Retrospective utilization review as a focused method of evaluation.

Retrospective UR may be the method of choice if, in general, a problem is best addressed through a sampling of completed records. Note that this type of review is currently different from a patient care evaluation or audit. Such studies usually compare optimum standards of care for a diagnosis with the actual care delivered to patients as documented in their records. Retrospective UR, however, may be used to focus on a problem in the delivery of care that has previously been identified. As such, it can be an effective component of a total quality assurance program.

Concurrent Review↗