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Biomedical subjects

S Spector

Publications and source records attributed to S Spector.

At least 91 records · Page 5Linked to original sources

Opioid polypeptides in guinea pig pancreas.

Extracts from guinea pig pancreas were found to contain high molecular weight enkephalin-containing polypeptides as well as free [Met]enkephalin and [Leu]enkephalin and the hexa-, hepta-, and octapeptides derived from proenkephalin. Within the limits of sensitivity of our assay (10 fmol/g of tissue), beta-endorphin and beta-lipotropin were undetectable.

Amino Acid Sequence

Disposition of drugs in man by radioimmunoassay.

The disposition of morphine and clonidine was investigated by means of radioimmunoassay. After the administration of a single i.v. dose of morphine (10 mg/70 kg) to 10 men who had not received other drugs for two weeks preceding the study, a multiphasic decline in serum concentrations of morphine occurred. Detectable blood concentrations of morphine, or a metabolite, or of both, persisted for up to 96 hours after a single i.v. dose. The radioimmunoassay for clonidine is capable of detecting as little as 10 pg of clonidine. The antibody fails to bind 2,6-dichlorophenylguanidine, a known metabolite of clonidine, while the other metabolite, 4-hydroxyclonidine, was as potent as clonidine in displacing labeled clonidine from the antibody. The disposition of clonidine ion plasma and tissues could be monitored by radioimmunoassay.

Binding Sites

Studies on the hypotensive response to atropine in hypertensive rats.

The hypotensive effect of atropine sulfate was evaluated in conscious, unanesthetized hypertensive rats (spontaneously hypertensive rats and Sprague-Dawley rats made hypertensive by s.c. implantation of deoxycorticosterone acetate, tablets) and their respective normotensive controls. In all animals, atropine (5-50 mg/kg i.v.) caused an immediate and dose-dependent decrease in blood pressure. However, the hypotensive response was of greater magnitude and of longer duration in the hypertensive rats. Pretreatment of the animals with phentolamine prevented the hypotension by atropine. Plasma concentrations of atropine were determined by radioimmunoassay and were identical in both hypertensive and normotensive rats. Atropine blocked the pressor responses to norepinephrine and shifted the dose-response curve for norepinephrine to the right to a similar extent in spontaneously hypertensive and Wistar-Kyoto rats. Thus, atropine acts as a competitive antagonist of norepinephrine and this action underlies its hypotensive effect. The greater responsiveness of hypertensive rats is not due to a difference in pharmacokinetic handling of atropine nor to a greater degree of blockade of the norepinephrine pressor response in vivo, but may result from the altered sympathetic tone in the hypertensive rats. Atropine may, in addition to its action on alpha adrenergic receptors, affect other systems such as calcium handling. It is speculated that an effect on this system may contribute to the longer duration of response seen in hypertensive rats.

Adrenal Medulla

A new radioimmunoassay for haloperidol: direct measurement of serum and striatal concentrations.

A sensitive and specific radioimmunoassay for haloperidol has been developed. Antibodies were elicited in rabbits immunized with haloperidol hemisuccinate coupled to bovine serum albumin. Optimum sensitivity was obtained with a 1:4000 dilution of the antisera, permitting the detection of as little as 2.6 ng/ml of haloperidol. Major metabolites of haloperidol did not cross-react in the assay. The method does not require an extraction procedure and can be performed using as little as a 5-microliter sample. Haloperidol levels in rat serum and striatum were determined with this method, after the i.v. administration of different dosages of the drug. The distribution and elimination of haloperidol was linear over the dose range to have an elimination half-life of approximately 2.6 hr at all three dosage levels.

Animals

Influence of clonidine on experimental hypertension induced by cholinergic stimulation.

Hypertension may be induced by pharmacologic activation of central cholinergic receptors either indirectly, through the injection i.v. of physostigmine, or directly, through the injection of i.v. of arecholine in anesthetized rats. Activation of peripheral preganglionic cholinergic receptors with dimethylphenylpiperazinium iodide (DMPP) also produced a hypertensive response. Pretreatment with various doses of clonidine caused inhibition of the pressor response to central cholinergic stimulation but was without effect on the response to ganglionic cholinergic stimulation.

Animals

Pharmacokinetics of d-tubocurarine in man: effect of an osmotic diuretic on urinary excretion.

The pharmacokinetics of d-tubocurarine (dTc) and the urinary excretion of dTc were studied in 18 neurosurgical patients with normal renal function, over a period of 96 hours. The effects of an osmotic diuretic (mannitol) on urinary elimination of dTc were determined. Following a single intravenous dose of d-tubocurarine (dTc, 0.3 mg/kg), serum levels and urinary excretion of the drug were measured. A specific radioimmunoassay was used for the analysis of dTc. Nine of the patients also received mannitol, 1 g/kg, after the injection of dTc for surgical indications. The study showed that only 45 per cent of the injected dose of dTc was excreted in 24 hours. Between 24 and 96 hours, an additional 7 per cent of the drug was excreted in the urine. The administration of mannitol, an osmotic diuretic, did not increase the excretion of dTc. The time-concentration relationship of serum concentration of dTc was analyzed. Using the four-exponential equation (data to 96 hours), the calculated volume of distribution (Vdarea) was 3.4 1/kg. This volume, which is greater than the volume of total body water, suggests that dTc is stored in certain tissues in the body and slowly released over a period of days to weeks.

Half-Life

Isolated brain microvessels: preparation, morphology, histamine and catecholamine contents.

A method for the rapid preparation of parenchymal microvessels from rat, rabbit and bovine brains is described. Light and electron microscopic examination of the isolated microvessels showed the smooth muscle and endothelial cells to be intact and substantially free of neutrophil contamination. The observation of 0.2 to 2.0 micron electron dense granules in the adventitial space associated with some of the isolated arteriolar elements and the identification of histamine in microvessel extracts is suggestive of the presence of mast cells in the microvessel preparations. Age-dependent changes in histamine content and an increased histamine content in microvessels from hypertensive rats were noted. Using a sensitive radioenzymatic assay, the catecholamine (CA) contents of microvessels isolated from cow, rat and rabbit were measured. The total CA contents of all microvessel preparations were small (< 0.35 microgram g-1) with norepinephrine being the predominant CA present. A large ratio of dopamine to norepinephrine was found in microvessels from rat and bovine brain. The possible origins of the CAs present in the isolated microvessels are discussed.

Animals