Biomedical subjects
Publications and source records attributed to S Spector.
Norepinephrine and the enzymes involved in its synthesis and degradation were found to be associated with isolated brain microvessels. The significance of these results are discussed with respect to adrenergic innervation of the cerebral microvessels and thereby neural regulation of the cerebral microcirculation.
Vascular tyrosine hydroxylase (TH) activity did not appear to be affected by the sex hormones. There were no differences in enzyme activity in the mesenteric artery or vein taken from male and female normotensive or spontaneously hypertensive rats. Castration of either male or female rats did not alter mesenteric artery or vein TH activity, and the administration of estradiol, progesterone, or testosterone also had no effect on vascular TH activity. However, the sex hormones did alter activity in other tissues. Estradiol and progesterone administration to intact female rats increased adrenal TH activity, whereas castration of the male rat decreased it. Although the sex hormones were not important regulators of TH in blood vessels, vascular TH activity did appear to be under some hormonal regulation since hypophysectomy decreased mesenteric artery enzyme activity. Hypophysectomy studies also indicated that adrenal TH activity was under some hormonal regulation.
An antibody to serotonin (5-HT) was tested on several preparations in which 5-HT is considered to be involved. The antibody was capable of effectively competing with 5-HT receptor sites for free molecules of 5-HT. It inhibited the uptake of 3H-5HT by blood platelets and may explain the reduced endogenous 5-HT concentration in blood platelets of immunized rabbits. The decreased platelet content of 5-HT was substantiated by electron microscopic studies which showed a reduction in the number of 5-HT-containing subcellular storage organelles in platelets from these animals. The 5-HT antibody inhibited the 5-HT-induced contraction of aortic strips in a tissue bath preparation. When given intraventricularly, it inhibited for a time the sedative actions of reserpine thus adding new evidence to the often postulated role of 5-HT in the actions of reserpine.
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Understanding of the pharmacology of the narcotic antagonist naloxone has been limited by the lack of a convenient and sensitive method of assay. A radioimmunoassay for naloxone has been developed and is described. It is applicable for drug analysis in either serum or brain. The limit of sensitivity of the assay was 0.1 ng. Naloxone glucuronide, noroxymorphone (nor-naloxone) and morphine were not recognized by the antibody whereas naltrexone and 6-hydroxynaloxone were able to displace naloxone-3H from the antibody. The assay was of sufficient sensitivity to follow the serum levels of naloxone in man for up to 2 hours after an i.v. injection of 0.4 mg. In animal studies, the biologic half-lives of naloxone or morphine (5 mg/kg) were compared after s.c. injection in rats. The peak serum levels A (1 mu/mo), time to peak serum levels (less than 1/2 hour), and serum half-life (40 minutes) were comparable. However, the brain entry and egress of the two compounds differed markedly. Peak brain levels of naloxone occurred within 15 minutes and had declined by 50% within 1 hour, whereas the peak brain levels of morphine were sustained for up to 2 hours. At peak serum levels, the brain/serum ratio for morphine was 0.1 whereas for naloxone it was 15 times greater. We suggest the high brain/serum ratio of naloxone contributes to its potency whereas the rapid egress from the brain is important in the short duration of action of naloxone.
This paper describes the production of antibodies against demethyl-imipramine (DMI). By using antisera, a radioimmunoassay was developed capable of detecting 0.2 ng of DMI which is linear up to 25 ng. The assay has been applied for the measurement of DMI in rat plasma and brain. The assay might find application especially when only limited amounts of blood, plasma or tissue are available.
The correlation between chlorpromazine (CPZ) levels in rat brain and serum with hypothermia was investigated. Even large differences between brain and serum concentrations of CPZ could be demonstrated at the two dosages of the drug investigated, the groups showed an identical hypothermic effect between 5 to 30 minutes, with maximum hypothermia being reached 1 hour. It also appears that when brain concentrations of CPZ were lower than 1 mug/g, body temperature returned to normal. We could not demonstrate any preferential uptake of CPZ into the hypothalamus, the proposed site at which CPZ acts to cause hypothermia.
The antihypertensive drugs, reserpine and hydralazine, produce different effects on tyrosine hydroxylase activity and norepinephrine levels in blood vessels and other tissues of the spontaneously hypertensive rat at doses which cause an equivalent reduction in blood pressure. Reserpine administration is associated with increased tyrosine hydroxylase activity in the mesenteric artery, mesenteric vein and adrenal, but the vasculature appears more sensitive to the effects of reserpine than the adrenal. This increase in tyrosine hydroxylase activity can be related to catecholamine depletion in the mesenteric artery, mesenteric vein and adrenal. Since chlorisondamine, a ganglionic blocking agent, diminished the ability of reserpine to increase tyrosine hydroxylase activity in the mesenteric artery and adrenal, it is likely that increased nerve activity is involved in regulation of the enzyme in both tissues. Hydralazine neither alters tyrosine hydroxylase activity in arteries or veins, nor depletes catecholamine levels in these tissues. In the adrenal, hydralazine increases tyrosine hydroxylase activity independently of any change in catecholamine levels. It would appear that changes in tyrosine hydroxylase activity produced by antihypertensive drugs are organ dependent and may involve both neuronal activity and amine depletion.
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Collagen synthesis is increased in the aortas, mesenteric arteries, and to a lesser extent, in the hearts of rats either made hypertensive with desoxycorticosterone acetate-salt or that are spontaneously hypertensive. Several markers of collagen biosynthesis were shown to be increased, including prolyl hydroxylase (EC 1.14.11.2; proline, 2-oxoglutarate dioxygenase), prolyl hydroxylase-related antigen, total collagen content, and the incorporation of [(3)H]proline into total protein and into collagen. The antihypertensive agents chlorothiazide and reserpine, when administered before the onset of hypertension in the rats treated with desoxycorticosterone acetate-salt, prevented or diminished the increase in collagen biosynthesis. When reserpine was given after the onset of hypertension, prolyl hydroxylase activity was decreased concomitant with the decrease in blood pressure. Treatment with reserpine is particularly effective in diminishing arterial prolyl hydroxylase activity.
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