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Biomedical subjects

I Smith

Publications and source records attributed to I Smith.

At least 325 records · Page 18Linked to original sources
PubMed1984

Tubular transport and metabolism of cimetidine in chicken kidneys.

Renal tubular transport and renal metabolism of [14C]cimetidine (CIM) were investigated by unilateral infusion into the renal portal circulation in chickens (Sperber technique). [14C]CIM was actively transported at a rate 88% that of simultaneously infused p-aminohippuric acid, and its transport was saturable. The following organic cations competitively inhibited the tubular transport of [14C]CIM with decreasing potency: CIM, ranitidine, thiamine, procainamide, guanidine and choline. CIM inhibited the transport of [14C]thiamine, [14C]amiloride and [14C]tetraethylammonium. During CIM infusion, two renal metabolites, CIM sulfoxide and hydroxymethylcimetidine, were found in urine. When CIM sulfoxide was infused, its transport efficiency was 32% and not saturable. CIM sulfoxide did ot inhibit the simultaneous renal tubular transport of p-aminohippuric acid or tetraethylammonium. CIM is transported by the organic cation transport system and the kidney metabolizes CIM. Transport of CIM and other cationic drugs could produce a drug interaction to alter drug excretion.

Animals↗
PubMed1983

Natural and synthetic analogues of melatonin and related compounds. I. Effects on the reproductive system of the male Syrian hamster.

The potential antigonadotrophic properties of a number of synthetic and natural melatonin analogues were examined. Adult male hamsters received daily subcutaneous injections (25 micrograms/animal/day) each afternoon for 7 or 10 weeks. The only analogue to possess antigonadotrophic activity similar to melatonin wa 6-chloromelatonin; melatonin and 6-chloromelatonin produced a significant reduction in both testicular and accessory sex organ weights, plasma LH and pituitary prolactin. These results suggest that, in the Syrian hamster, 6-chloromelatonin acts as a melatonin agonist and may be of use to elucidate further the physiological role of melatonin.

Animals↗
PubMed1983

Acyltryptophols reversibly inhibit muscle contractions caused by the actions of acetylcholine and raised potassium ion concentrations.

1. Acetylmethoxytryptophol, originally isolated from the pineal gland, inhibits both the nicotinic and muscarinic receptor stimulatory activities of acetylcholine on frog rectus muscle and guinea pig ileum. 2. Synthetic homologues and analogues, including the acetyl-, propionyl-, butyryl-, and valeryl-methoxytryptophols, tryptophols and alpha-methyl-tryptophols have been prepared and shown to possess similar activity on the frog muscle, with butyryl compounds being the most active. Methoxytryptophol, tryptophol, alpha-methyltryptophol and acetylhydroxytryptophol possess little or no activity. 3. All acyltryptophols tested inhibit the effect of increased potassium concentrations on frog muscle. 4. It is concluded that the acyltryptophols act not at the transmitter receptor level but either at the potassium ion channel or elsewhere in the cell membrane.

Acetylcholine↗
PubMed1983

Acyltryptophols reversibly inhibit the uptake of thymidine after phytohaemagglutinin transformation of human lymphocytes.

1. Lymphocytes were stimulated for 72 hours with phytohaemagglutinin (PHA), [3H]-thymidine was added and, after a further 4 hours incubation, its uptake into DNA was measured. 2. Addition of acetylmethoxytryptophol (aML) and other acyl tryptophols simultaneously with the PHA caused an immediately reversible, dose-dependent reduction in uptake of thymidine into the DNA. 3. Similar additions one hour before the addition of thymidine had identical, immediately-reversible effects. 4. Similar addition up to about 30 min after the addition of thymidine showed a reduced but still dose-dependent effect on the amount of DNA radioactivity. 5. It is concluded that aML, and related acyltryptophols, act by inhibition of thymidine uptake into the lymphocyte, in which case the compounds probably dissolve in the lipid bilayer of the membrane and act as channel blockers.

Cells, Cultured↗
PubMed1983

Day/night rhythmicity in the methylating capacities for different 5-hydroxyindoles in the pineal, the retina and the Harderian gland of the golden hamster (Mesocricetus auratus) during the annual seasons.

In the pineal, the Harderian gland and the retina of the golden hamster the day/night capacity for the synthesis of different methoxyindoles is investigated under natural conditions for one 24-hour period in the months of December, March and June. The amounts of the methoxyindoles and the diurnal rhythms in the synthesis are different in the various months during which the tests were performed. There is a striking increase in the synthesis of melatonin and methoxytryptophol in all three organs in June as compared with December. Equally striking is the high synthesis of methoxytryptamine in the pineal in June, whereas this compound was not formed in the Harderian gland and the retina in this month. Methoxytryptophan synthesis was not observed in June in any of the three organs. Methoxyindoleacetic acid rhythmicity shows a pattern more or less identical to that of melatonin and methoxytryptophol. A high synthesis exists at the end of the June day, but greater fluctuations during the days of the two other months. Acetylmethoxytryptophol is synthesized in the pineal during the night in March, but in the late afternoon in June. The largest quantity of this compound is found in the Harderian gland in December, in the pineal in March and in the retina in June. The largest amounts of melatonin and methoxytryptophol are synthesized when gonadal weight is largest. The possible correlation between the amounts synthesized, the rhythmicities in synthesis and the reproductive system is discussed.

Acetylserotonin O-Methyltransferase↗
PubMed1983

Natural and synthetic analogues of melatonin and related compounds. II. Effects on plasma thyroid hormones and cholesterol levels in male Syrian hamsters.

Synthetic or natural analogues of the pineal indole, melatonin, were injected separately every evening (1700 hours) for 7 (Exp. 1) or 10 (Exp. 2) weeks into adult male Syrian hamsters maintained in 14 hours of light and 10 hours of darkness each day. Plasma thyroxine (T4) levels were significantly depressed by 25 micrograms/day of melatonin (aMT) in both experiments. Injecting 25 micrograms/day either of acetyl methoxytryptophol or of synthetic analogues (hexanoyl methoxytryptamine, propionyl methoxytryptophol, or 6-chloro-melatonin) in Exp. 1 or of a natural analogue (N-acetylserotonin, 6-hydroxy-melatonin, hydroxytryptophol, or methoxytryptophol) in Exp. 2 had no effect on the circulating T4 levels. Plasma levels of triiodothyronine (T3) and thyrotropin (TSH) were unaffected in either experiment. Since none of the tested melatonin analogues is capable of suppressing circulating T4 concentration when given in a dose at which melatonin is reproducibly effective, the pineal-induced suppression of T4 is most likely mediated by melatonin. Plasma cholesterol levels were elevated only in hamsters receiving 6-chloromelatonin injections. However, plasma triglyceride levels were significantly higher than the diluent treated controls in Exp. 1 after injections of melatonin, acetyl methoxytryptophol, propionyl methoxytryptophol and 6-chloromelatonin. Interscapular brown adipose tissue was significantly heavier in melatonin treated animals.

Animals↗
PubMed1983

The influence of GABA on the synthesis of N-acetylserotonin, melatonin, O-acetyl-5-hydroxytryptophol and O-acetyl-5-methoxytryptophol in the pineal gland of the male Wistar rat.

The influence of GABA on the synthesis of N-acetylserotonin, melatonin, O-acetyl-5-hydroxytryptophol and O-acetyl-5-methoxytryptophol has been investigated using different experimental procedures. It was demonstrated that when GABA and an acetyl donor were added to the incubation medium together, a significant increase in synthesis of the N-acetylated products occurred during the night. Moreover there was a large increase in N-acetylserotonin synthesis at 15(00) hrs although none was observed in the control experiments. However, when GABA was added 20 min before the acetyl donor, synthesis of the N-acetylated products was significantly less. The opposite effect was observed for the O-acetylated indoles. These results confirm the proposal by Ebadi et al. (1982) that GABA, like norepinephrine, may be a regulator of melatonin synthesis. As melatonin is implicated in the regulation of reproduction it may be that GABA is equally significant in this regulatory effect.

Acetylation↗
PubMed1982

Low-frequency voltage noise in a mammalian bone cell clone.

Measurements were made of plasma membrane voltage noise in cells of a bone cell clone. The measurements were made under conditions intended to approximate in vivo conditions more closely than in previous electrical measurements on small mammalian cells. Mononucleate cells of normal size, imbedded in a collagen matrix, were used. The electrical state of the cell membrane under normal conditions was characterized by low-frequency random fluctuations (noise) of high magnitude. Hyperpolarizing spikes were observed in some cells. Power spectrum analysis revealed that the random fluctuations were actually a sum of incoherent spike patterns, with spikes of the same time width as those seen in the clearly spiking patterns. This analysis, combined with similar measurements in a high [K+], low [Na+] medium, showed that the fluctuation/spiking phenomenon resulted from modulation of K+ and Na+ transport by a control process at a level higher than that of the individual channels. This process persisted when the membrane potential was depolarized. These results indicate that the membrane potential is not part of the feedback loop producing the fluctuation/spiking phenomenon.

Animals↗
PubMed1982

The effect of melatonin and other indole derivatives in maintaining ovulation in rats kept in continuous light and the influence of these indoles on HIOMT activity in the pineal gland.

The aim of the present study was to investigate whether the ovulation-maintaining effect of melatonin in rats, exposed to continuous light (LL), was also exerted by other pineal indoles which have been reported to influence the reproductive processes of mammals. The effect of 10 micrograms melatonin was compared with that of similar amounts of either N-acetylserotonin, 5-methoxytryptophol, 5-methoxyindole-3-acetic acid, 5-hydroxytryptophol, 5-methoxytryptamine or 5-methoxytryptophan. All these compounds appeared to be significantly less effective than melatonin in preventing the effect of LL, ovulation being preserved in only 20--33% of the rats investigated, with melatonin this percentage being 60--75%. Investigations were also carried out to assess the effect of these indole derivatives on HIOMT (hydroxyindole-O-methyl transferase) activity in synthesizing different 5-methoxyindoles in the abnormally influenced pineal gland due to LL. Melatonin, the compound the effect of which on ovarian cyclicity is strongest, stimulates 5-methoxytryptophol synthesis; while other less active compounds stimulate the synthesis of melatonin and inhibit that of O-acetyl-5-methoxytryptophol. The possibility that the effect of other indoles than melatonin on ovarian cyclicity might be due to stimulation of melatonin synthesis was considered. A possible functional relationship of the different indoles cannot be excluded.

Acetylserotonin O-Methyltransferase↗
PubMed1982

The role of platelet surface proteins reacting with heterologous antibodies.

Platelets were labeled with surface-labelling agents which identified up to six platelet membrane proteins. Three of these labelled proteins were recognised by a specific anti-platelet membrane serum by immunoprecipitation. Affinity fractionation of platelets with insolubilised IgG obtained from the anti-platelet membrane serum indicated a greater reaction between the antiserum and the platelet surface. Fab fragments from the antiserum inhibited ristocetin-induced aggregation of platelets and partially inhibited collagen-induced aggregation but did not affect ADP aggregation. Crossed immunoelectrophoresis of platelets using the anti-platelet membrane serum showed that the antiserum was specific for platelet membranes.

Animals↗
PubMed1981

Changes in the circadian rhythmicity of N- and O-acetyltransferase activities in the pineal gland of 38 day old male wistar rats when examined under white, red and green light.

N-acetyltransferase activity was quantified in the pineal gland of 38 day-old male Wistar rats under different experimental conditions. Under daily white light/dark photoperiods (12 L : 12 D), N-acetyltransferase activity showed a peak of activity at midnight for the synthesis of both N-acetylserotonin and melatonin. Using red light instead of white light a shift of the enzyme activity involved in the production of both compounds towards the preceding light period was observed. Using green light instead of white light the enzyme activity shifted to later periods. Under white light/dark conditions pineal O-acetyltransferase activity when quantified was maximal during the early hours of the night. With periodic red light this maximal activity was extended over a longer period including late hours of the preceding day and later hours of the night. Periodic illumination with green light caused a peak of activity at midnight and an increase of activity at then end of the dark period. A possible relationship between previous results obtained on the influence of pterins on HIOMT activity and the effects of light on reproduction is discussed.

Acetyltransferases↗
PubMed1981

Cloning of an early sporulation gene in Bacillus subtilis.

A 0.8-megadalton BglII restriction fragment of Bacillus licheniformis cloned into the BglII site of plasmid pBD64 can complement spo0H mutations of Bacillus subtilis. The clone was isolated by selecting for the Spo+ phenotype and antibiotic resistance, using the helper system described by Gryczan et al. (Mol. Gen. Genet. 177:459-467, 1980). The insert is functional in both orientations and thus presumably has its own promoter. A deletion generated within the 0.8-megadalton insert by HindIII restriction and subsequent religation eliminates the ability of the cloned fragment to complement spo0H mutations. The cloned B. licheniformis deoxyribonucleic acid segment specifies the synthesis, in minicells, of a polypeptide of approximately 27,000 daltons. This protein is observed with both orientations, but not when the HindIII deletion is present in the cloned B. licheniformis chromosomal fragment. We have also demonstrated that ribonucleic acid complementary to the cloned B. licheniformis sporulation gene is transcribed in B. licheniformis both during vegetative growth and sporulation.

Bacillus↗