[Sulfonylurea receptors].
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ATP-Binding Cassette Transporters↗
Biomedical subjects
R Huupponen
Publications and source records attributed to R Huupponen.
Systemic effects of ocular drugs.
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Administration, Topical↗
Activity of hepatic glucose phosphorylating and NADPH generating enzymes in Zucker rats.
The activities of hepatic enzymes involved in glucose phosphorylation and NADPH production were studied in male and female obese Zucker rats (fa/fa) and lean control animals (Fa/-). The fa/fa animals were heavier and had higher serum insulin levels than the lean rats. The glucokinase activity and the total glucose phosphorylation capacity were also higher in the obese animals. The activity of glucokinase correlated significantly with serum insulin levels. The glucose-6-phosphate phosphohydrolase activity was unchanged or slightly lowered in the obese rats. The activity of malic enzyme was elevated in the obese animals.
Animals↗
Systemic absorption of topically applied ocular atropine.
We quantitated atropine plasma levels and monitored blood pressure, heart rate, and salivary secretion after ocular application. Eight patients received 40 microliters 1% atropine in the lower cul-de-sac of one eye in connection with ocular surgery. Atropine plasma levels were determined for 90 minutes by radioreceptor assay. The peak plasma atropine concentration of 860 +/- 402 pg/ml was reached within 8 minutes in all patients. The ocular absorption of atropine was at least as rapid as that reported for intramuscular administration. Ocular atropine did not affect patients' blood pressure or heart rate when compared with those of the placebo group. Thirty minutes after administration of atropine eyedrops, the salivary secretion in the experimental group was reduced, but was statistically insignificant from the placebo group.
Adult↗
Somatostatin concentrations in discrete hypothalamic nuclei of genetically obese Zucker rats.
Hypothalamic somatostatin concentration was determined in 6.5 to 9 months old male and female genetically obese fatty (fa/fa) and lean (Fa/-) Zucker rats. Similar somatostatin levels were found in fatty and lean animals in the hypothalamic regions previously known to contain the highest hormone levels (median eminence and arcuate, periventricular and ventromedial nuclei). The fatty animals were grossly obese and had a pronounced hyperinsulinemia.
Animals↗
Timolol binding to bovine ocular melanin in vitro.
The binding characteristics of 3H-timolol to bovine iris melanin were determined by using a ligand binding assay. The association and dissociation kinetics were performed using 100 nM 3H-timolol and 0.5 mg/ml melanin at 37 degrees C. The effects of pH, ethanol, 2.5 microM isoxuprine and 1 microM d- and 1-propranolol on 100 nM 3H-timolol binding were also determined. In saturation experiments 3H-timolol (from 1.25 nM to 5 microM) was equilibrated with 0.5 mg/ml melanin. The binding was saturable with the binding maximum of about 1 microM timolol/g melanin. The binding of 100 nM 3H-timolol to melanin increased up to 5 hours and amounted 24% of the added radioactivity. The best fit of the association constants was obtained by using a two fit model. The association rate constants were 4.92 x 10(5) M-1 min-1 and 5.95 x 10(6) M-1 min-1. The dissociation was rapid in vitro and uniphasic with a dissociation rate constant of 5.08 x 10(-3) min-1. The pH, ethanol and both enantiomers of propranolol did not appreciably alter the timolol binding, while isoxuprine diminished it.
Animals↗
Debrisoquine oxidation in a Finnish population: the effect of oral contraceptives on the metabolic ratio.
1. The debrisoquine hydroxylation phenotype was assessed in 211 healthy subjects of Finnish Caucasian origin. 2. A bimodal distribution was observed in the urinary debrisoquine/4-hydroxydebrisoquin ratio. Eleven subjects (about 5%) were poor metabolizers of debrisoquine, when a ratio of 12.6 was used as the cut-off point. 3. The mean metabolic ratio of 35 extensive metabolizers taking oral contraceptives was slightly lower than that of extensive metabolizers not taking contraceptives. This indicates that oral contraceptives may change the phenotyping near the metabolic ratio of 12.6. 4. The metabolic ratios were determined in eight subjects using both 4 h and 6 h urine collection times. The metabolic ratios corresponded well with each other indicating the usefulness of the shorter 4 h collection time.
Adult↗
Significance of insulin receptors in the action of sulphonylurea drugs.
The mechanisms by which sulphonylureas lower blood glucose are complex. Sulphonylureas increase insulin secretion and possibly also decrease glucagon release from the pancreas. In the periphery, they increase insulin binding to its receptors through direct or indirect mechanisms, primarily by increasing receptor number. Sulphonylureas also potentiate the action of insulin in peripheral glucose uptake and metabolism, even when no measurable effects on insulin receptors can be demonstrated. This post-receptor mode of action seems to play an important role in the spectrum of sulphonylurea effects.
Animals↗
The pharmacokinetics of ocularly applied timolol in rabbits.
[3H]timolol derived radioactivity and beta-antagonistic activity in the aqueous humour, iris, ciliary body and blood in rabbits were analyzed by liquid scintillation counting (LSC) and radioreceptor assay (RRA) after ocular timolol. After ocular application of tracer labelled timolol, the radioactivity decreased slowly in the iris (Kel = 0.05 h-1) and ciliary body (Kel = 0.02 h-1). In the aqueous humour the elimination rate was faster (Kel = 0.57 h-1). The beta-antagonistic activities of the aqueous humour and plasma decreased rapidly when compared to LSC values. The ethanol extractable pool of the beta-antagonistic activity from the iris and ciliary body was only a few percent of the corresponding LSC estimates. The kinetics of beta-antagonistic activity extractable from iris and ciliary body was identical with that in the aqueous humour. Timolol concentrations in the untreated rabbit eye were sufficiently high to lower the intraocular pressure.
Animals↗
Evidence for the involvement of the opiate-receptors in the diazepam-induced human growth hormone secretion.
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Adult↗
Effects of eyelid closure and nasolacrimal duct occlusion on the systemic absorption of ocular timolol in human subjects.
Eyelid closure and nasolacrimal occlusion may decrease the systemic absorption of topically applied drugs. We studied the absorption kinetics of 20 microliter 0.5% timolol eyedrops in eight healthy volunteers. Each subject was supine for 30 minutes after the drug application. In randomized order, the volunteers kept their eyelids closed (ELC), or applied nasolacrimal occlusion (NLO) or blinked normally. Blood samples were drawn up to 90 minutes and analyzed for timolol with a radioreceptor assay. There was great interindividual variation in the timolol absorption. NLO reduced the total timolol absorption, but in some subjects the initial absorption was also enhanced by this procedure.
Absorption↗
The effect of guar gum on the acute metabolic response to glyburide.
The effect of 5 g guar gum on the acute blood glucose, insulin and C-peptide response to 5 mg glyburide (HB 419) was investigated in 10 healthy volunteers after an overnight fast. The co-administration of guar gum significantly enhanced the insulinogenic and blood glucose lowering effect of glyburide.
Adult↗
Effect of the blood glucose level on the metabolic response of intravenous salbutamol.
The effect of an intravenous salbutamol dose (2 micrograms/kg or 8 micrograms/kg) on serum insulin and blood glucose was studied in 8 healthy volunteers after different glucose loads. Administration of glucose significantly increased circulating blood glucose and serum insulin concentrations before the salbutamol injection. The acute insulin releasing capacity of 2 micrograms/kg salbutamol was intensified and its blood glucose elevating effect was diminished by preceding glucose loading. Elevation of salbutamol dose from 2 to 8 micrograms/kg caused a 3.4 fold elevation of insulin secretion and an even more pronounced increase in blood glucose response.
Albuterol↗
Effect of guar gum on glipizide absorption in man.
The effect of 4.75 g guar gum, a fibre preparation, on the absorption of 2.5 mg glipizide has been studied in 10 healthy volunteers given a standard breakfast. Three different experimental protocols were used: glipizide without guar gum (Treatment 1), glipizide with guar gum (Treatment 2) and guar gum 30 min after the drug together with breakfast (Treatment 3). The serum glipizide at 30 minutes was higher during Treatment 2 than Treatment 3 (p less than 0.01), but neither differed from the control treatment. The AUCs for glipizide were calculated up to 8 hours. They did not differ significantly between the treatment, although there was a non-significant trend to lower values during Treatment 3. Serum insulin and blood glucose levels were determined up to 3 h. Corresponding to differences in the glipizide concentration, serum insulin was highest and blood glucose lowest at 30 minutes during Treatment 2. According to this single dose study, guar gum does not have any substantial deleterious effect on the absorption of glipizide. The lack of effect may be due to the complete gastrointestinal absorption of glipizide.
Adult↗
Effects of apomorphine on blood levels of homovanillic acid, growth hormone and prolactin in medicated schizophrenics and healthy control subjects.
Two doses of apomorphine (0.005 mg/kg as a subcutaneous injection and 0.015 mg/kg as a 90 min i.v. infusion), and corresponding placebo treatments, were administered to 11 chronic medicated schizophrenic patients and to 8 healthy control subjects. The purpose of the study was to asses the usefulness of drug-induced alterations in the concentration of homovanillic acid (HVA) in plasma as indicators of dopamine autoreceptor sensitivity in the central nervous system. Growth hormone and prolactin in serum were also measured and used as indicators of postsynaptic dopaminergic drug effects. In the control subjects, i.v. apomorphine increased growth hormone in serum from 1.8 +/- 0.2 to 28.3 +/- 4.6 ng/ml and reduced prolactin by 57 +/- 7%. In the patients, apomorphine caused only weak neuroendocrine effects. HVA in plasma was not affected by apomorphine in either group of subjects. The results for growth hormone and prolactin indicate that postsynaptic dopamine receptors in the tubero-infundibular system are antagonized to a considerable degree also during chronic treatment with neuroleptics. The lack of effect of apomorphine on HVA levels suggests that HVA in plasma is not a sensitive indicator of the inhibition of dopamine release caused by small doses of apomorphine and mediated through dopamine auto-receptors. Supersensitivity of this class of receptors could not be demonstrated in our patients, which contrasts with some earlier results.
Adult↗
Apomorphine does not affect the basal insulin secretion in humans.
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Apomorphine↗
Systemic absorption of topically applied ocular timolol.
Symptoms and findings arising from the systemic beta blockade caused by topical ocularly applied timolol appear shortly after drug application. We studied the systemic absorption of 20 microliters of 0.5% timolol instilled unilaterally in the lower conjunctival cul-de-sac in 6 volunteers. At 3 min one subject, at 5 min three and at 8 min all but one showed measurable (greater than or equal to 215 pg/ml) timolol concentrations in the plasma. The rapid systemic absorption of topically applied ocular timolol observed in our study is consistent with the rapid appearance of the cardiovascular and pulmonary side effects reported in connection with timolol eye drop therapy.
Adult↗
Transient corneal anaesthesia after topical pindolol in rabbits.
The acute corneal anaesthetic potency of 0.5% pindolol eye drops was compared with that of 2% lidocaine and placebo solutions in 10 rabbits. Pindolol produced a rapid-onset anaesthetic effect similar to that of lidocaine, whereas placebo drops were without effect. The chronic effect of 0.25% pindolol, 0.5% timolol and placebo eye drops on corneal sensitivity were evaluated weekly for 1 month in rabbits. None of the solutions affected the basal corneal sensitivity, but pindolol eye drops caused a slight corneal anaesthesia, when tested at 10 min after application, especially during the first weeks of therapy. The effect of timolol was qualitatively similar, but much weaker and not statistically significant.
Anesthetics, Local↗