Biomedical subjects

A S Undie

Publications and source records attributed to A S Undie.

5 recordsLinked to original sources

PubMed1992

Selective dopaminergic mechanism of dopamine and SKF38393 stimulation of inositol phosphate formation in rat brain.

We have previously reported that dopamine and the D1 receptor-selective agonist, SKF38393, stimulate the formation of inositol phosphates in rat brain slices (Undie and Friedman, 1990, J. Pharmacol. Exp. Ther. 253, 987). The present experiments were conducted to determine if actions at alpha-adrenoceptors or at serotonergic sites may contribute to, or interact with, the observed stimulation of phosphoinositide hydrolysis by dopamine receptor agonists. Rat striatal slices prelabeled with [3H]inositol were treated with up to 500 microM dopamine, norepinephrine, serotonin (5-HT), or the dopamine D1 receptor agonist, SKF38393, and accumulated inositol phosphates determined. The action of norepinephrine was dose-dependently blocked by the selective alpha 1-adrenoceptor antagonist, prazosin, but not by SCH23390. The actions of dopamine and SKF38393 were dose-dependently blocked by the dopamine D1 receptor antagonist, SCH23390, but not by prazosin. The effects of 5-HT were blocked by the nonselective 5-HT antagonist, methiotepin, the selective 5-HT2 antagonist, ketanserin, the mixed 5-HT2/5-HT1C antagonist, mianserin, and, with much less potency, by the selective 5-HT1C antagonist, mesulergine. On the contrary, the serotonin receptor antagonists did not block the response to SKF38393, and there was no dose-dependent blockade of the 5-HT response by SCH23390. These observations indicate that the actions of dopamine and SKF38393 in stimulating inositol phosphate formation are selectively mediated through a D1-like dopamine receptor.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1990

Stimulation of a dopamine D1 receptor enhances inositol phosphates formation in rat brain.

Accumulation of inositol phosphates was determined in rat brain slices prelabeled with 2-[3H]inositol and incubated with various drugs. In the striatum, micromolar concentrations of dopamine, apomorphine and SKF38393 induced significant accumulations of inositol phosphates in a dose-dependent manner, whereas quinpirole lacked effect. The EC50 values for the accumulation of inositol monophosphate induced by dopamine, apomorphine and SKF38393 were, respectively, 148, 159 and 129 microM. SKF 38393 effect was time-dependent on the accumulation of all three inositol phosphates, with peak effects occurring 64-128 min after drug addition. The action of the dopamine D1 receptor agonist, SKF38393, was blocked by SCH23390 (D1-selective antagonist), but not by sulpiride (D2-selective antagonist), atropine (muscarinic antagonist), prazosin (alpha-1 adrenoceptor antagonist) or methiotepin and methysergide (serotonergic antagonists), indicating that the observed effects of dopaminergic agonists were selectively mediated through the D1 dopamine receptor. On examining the effect of SKF38393 in several brain regions, the highest dopaminergic stimulation of inositol phosphates formation was obtained in the amygdala, followed by the hippocampus and then the striatum and frontal cortex. The finding of an SKF38393-stimulated PI hydrolysis in amygdala, a brain region that is enriched in SCH23390 and SKF38393 binding sites but devoid of dopamine-stimulated adenylate cyclase, suggests that the D1 receptor that is linked to PI metabolism is independent of the D1 receptor which stimulates cyclic AMP formation.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1988

Differences in the cataleptogenic actions of SCH23390 and selected classical neuroleptics.

In an attempt to understand the nature of the interactions between D1 and D2 dopamine subsystems as well as between dopamine and acetylcholine, catalepsy was assessed in rats following various drug treatments. The D1-specific antagonist SCH23390 (0.1 mg/kg) produced prompt, potent and brief (less than 90 min) catalepsy with an ED50 of 0.105 mg (0.3 mumol)/kg. Conversely, fluphenazine (0.1 mg/kg), spiroperidol (0.1 mg/kg), and haloperidol (0.2 mg/kg) all had comparably potent but more slowly rising and prolonged (greater than 240 min) effects. The action of SCH23390 was synergistic with spiroperidol, inhibited by apomorphine or atropine, unaffected by mecamylamine, and markedly potentiated by pilocarpine. However, pilocarpine was unable to significantly potentiate the action of fluphenazine or spiroperidol. It is inferred that SCH23390 differs from the classical neuroleptics in its mechanism of cataleptogenicity, that there is a cholinergic link with the D1 dopamine system, and further, that there may be a difference in the nature or impact of the cholinergic interaction with the D1 and D2 dopamine systems.

Animals↗

PubMed1986

Pharmacological evaluation of Dioscorea dumetorum tuber used in traditional antidiabetic therapy.

This study was undertaken to confirm or otherwise disprove the alleged effectiveness of Dioscorea dumetorum tuber in the traditional treatment of clinical diabetes mellitus. Hydroalcoholic extracts of the tuber were fractionated by precipitation or solvent partition and the various extracts or fractions subjected to phytochemical and pharmacological tests. Whereas the alkaloid-containing fraction was hyperglycaemic in fasting normal mice, the whole extract and the fractions containing steroidal derivatives evinced significant hypoglycaemic activities in fasting normal mice or rabbits and in fasting alloxan-diabetic rabbits. The hypoglycaemic action of the glycosidic portion in particular was prompt and potent, in normal as well as in severely alloxan-diabetic rabbits suggesting thereby the possibility of obtaining an agent that could act in conditions of even severe insulin lack.

Animals↗

PubMedDate not supplied

Aging-induced decrease in dopaminergic-stimulated phosphoinositide metabolism in rat brain.

Accumulation of [3H]inositol phosphate and [3H]inositol labeling of phosphoinositides were evaluated in brain slices of 3-, 6-, 12-, and 24-month-old Fischer-344 rats. The dopamine agonist, SKF38393, stimulated significantly lower accumulations of inositol trisphosphate, inositol bisphosphate, and inositol monophosphate in the striatum, hippocampus, and frontal cortex of 24-month-old rats compared with the 6-month-old animals. No differences, however, were observed between the 3, 6, and 12-month-old groups. Furthermore there were marked decrements of 41% to 58% in the labeling of phosphoinositides in the different brain regions of the aged animals. Dose-response studies in forebrain slices of the 6-month-old and 24-month-old animals showed aging-related decrements of 53% (p less than 0.001) and 48% (p less than 0.001) in the maximal SKF38393-stimulated labeling of phosphoinositides and accumulation of inositol phosphates, respectively. These data suggest that aging of the rat brain is associated with alterations in the basal turnover of the inositol cycle and in the sensitivity of the transduction pathway to dopamine receptor stimulation.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗