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Biomedical subjects

C G Persson

Publications and source records attributed to C G Persson.

At least 217 records · Page 12Linked to original sources

An in vitro comparison of beta-adrenoceptor stimulants on potassium-depolarized uterine preparations from guinea-pigs.

1 A comparison of six beta-adrenoceptor stimulants has been carried out on in vitro preparations of guinea-pig uterus which were depolarized in K(+)-Krebs solution. Results have also been obtained on uterine preparations in which contractions to acetylcholine were inhibited. The establishment of the conditions for the K(+)-depolarized preparations are described.2 There was no significant difference between potency values (mean neg log EC(50) values) for any of the drugs on the two types of uterine preparation i.e. the preparations had the same sensitivity to the drugs.3 There was a less than two-fold difference between the relative potency values for the beta-adrenoceptor stimulants on the two types of uterine preparation. The relative potency values (isoprenaline = 100) on the K(+)-depolarized preparation were fenoterol 74.1, salbutamol 15.1, rimiterol 13.5, terbutaline 8.2 and orciprenaline 5.6.4 The relative potency values obtained on uterine preparations were less than three-fold different from those previously found for guinea-pig trachea (after inhibition of extraneuronal uptake).5 The pA(2) value for propranolol on the K(+)-depolarized uterine preparations was 9.13.6 It is concluded that the K(+)-depolarized guinea-pig uterine preparation can be used for quantitative studies on beta-adrenoceptor stimulant drugs. It lacks spontaneous activity, drugs can be added cumulatively and several drugs can be compared on a single preparation. In addition, the results obtained support the classification of the beta-adrenoceptors in guinea-pig uterus and trachea in the same sub-group (beta(2)).

Adrenergic beta-Agonists↗

Beta-adrenoceptor mediated inhibition by terbutaline of histamine effects on vascular permeability.

1 In guinea-pigs, previously given Evans blue dye intravenously, 13 to 18 intradermal injections of histamine, with or without other drugs, were made into the depilated trunk skin. Dye was then quantitatively extracted from each skin area and the measured absorbance values were used as a measure of vascular leakage of macromolecules. 2 Histamine (0.5 to 12 nmol) produced dose-related increased in vascular leakage. These were reduced by terbutaline (1 and 10 nmol) which produced a significant shift in the histamine dose-response lines to lower absorbance values. The effect of 0.1 nmol of terbutaline was significant only against doses of histamine of less than 2 nmol. 3 Propranolol (1 nmol and 10 nmol) antagonized the effects of terbutaline. Propranolol, at a dose of 10 nmol but not 1 nmol, itself reduced the responses to 1.5 nmol histamine. 4 We conclude that the inhibition by terbutaline of histamine-induced dye leakage in guinea-pig skin is mediated by stimulation of beta-adrenoceptors and its is suggested that this effect of terbutaline occurs directly on beta-receptors at the vascular leakage site.

Animals↗

Terbutaline preventing permeability effects of histamine in the lung.

In unanaesthetized guinea-pigs the effect of terbutaline on histamine-induced increase in lung weight was studied. Terbutaline 0.1 mg/kg and 0.3 mg/kg was given subcutaneously 5 min. before exposure during 60 min. to a histamine aerosol. Terbutaline markedly prevented the histamine-induced increase in lung weight. This effect is discussed in relation to the mechanism of action of mediator-induced increase in vascular permeability.

Animals↗

Effects of prostaglandins on the isolated human bladder and urethra.

The effects of prostaglandins F2 alpha (PGF2 alpha), E1 (PGE1) and E2 (PGE2) on the human lower urinary tract were studied in vitro in preparations obtained from patients undergoing total cystourethrectomy because of bladder malignancy. Tissue specimens were taken from different parts of the urethra, the urethrovesical junction, and the bladder. From these specimens, smooth muscle preparations were dissected and mounted in organ baths, that were filled with Krebs solution (37 degrees C) and bubbled with carbogen. Isometric tension was recorded. Preparations from the bladder and all parts of the urethra were contracted by PGF2 alpha. This effect was not affected by tetrodotoxin, phenoxybenzamine, or atropine; isoprenaline relaxed the PGF2 alpha induced contractions. PGE1 and PGE1 both contracted strips from the bladder. However, urethral preparations contracted by PGF2 alpha or noradrenaline were relaxed by these agents. This relaxing effect was at least as pronounced as that produced by isoprenaline; it was not affected by propranolol.

Aged↗

Adrenergic and Cholinergic Nerves of the Human Urethra and Urinary Bladder. A histochemical study.

The occurrence and distribution of adrenergic and acetylcholine esterase (AChE) positive nerves in the human urethra and urinary bladder were studied histochemically with the fluorescence method of Falck and Hillarp, and the copper thiocholine method of Koelle and Friedenwald. Both types of nerves were mainly confined to the layers of smooth muscle cells in the walls of the organs. In all parts of the urethra, there was a scanty supply of adrenergic nerves. Few adrenergic nerves were also found in the urinary bladder, except in the trigone area, where they were abundant. AChE-positive nerves were uniformly and richly distributed in the urinary bladder. Throughout the urethra the distribution of AChE-positive nerve fibres was uniform, but the number was clearly less than in the urinary bladder. No intrmurally located adrenergic or AChE-Positive ganglion cells could be demonstrated.

Acetylcholinesterase↗

Diagnostic and therapeutic aspects of urge urinary incontinence in women.

Under standardized conditions, simultaneous urethrocystometry and recording of urethral pressure profile were performed in 10 healthy volunteers and 20 patients suffering from urge incontinence. In the normal subjects, desire to void occurred at a bladder volume of about 300 cm3. At maximum bladder capacity (approximately 500 cm3), variations in intraurethral pressure were recorded at a time when the intravesical pressure remained stable. Immediately before voiding, there was a marked reduction in intraurethral pressure and then the intravesical pressure increased. In 10 of the patients with symptoms of urge incontinence, the findings did not differ from those in the normal subjects. In the other 10 patients, urgency was reported at bladder volumes between 125 and 150 cm3, and the maximum bladder capacity did not exceed 200 cm3. In 8 of them, marked variations in intraurethral pressure were recorded when urge was experienced, whereas the bladder pressure remained stable. In 2 of the patients, variations in intraurethral and intravesical pressure occurred simultaneously. The role of the urethra in urge incontinence is discussed.

Adult↗

Respiratory and cardiovascular effects of 3-methylxanthine, a metabolite of theophylline.

The effects of 3-methylxanthine (3-MX), a major metabolite of theophylline in man, were studied and compared with those of theophylline in isolated preparations of human and guinea-pig airways, isolated guinea-pig hearts, and in anaesthetized cats. 3-MX was pharmacologically active, producing effects similar to those of theophylline. The guinea-pig and human airways preparations were relaxed; the rate and force of contraction of guinea-pig hearts were increased. In anaesthetized cats, 3-MX decreased the respiratory overflow and arterial blood pressure, and increased the heart rate. Theophylline was always more potent (between 1 and 5 times) than 3-MX. It is suggested that 3-MX may contribute to the effects of theophylline during long-term treatment.

Animals↗

Inhibitory innervation of cat sphincter of Oddi.

1 Electrical stimulation with trains of 0.1-0.2 ms pulses of the cat isolated sphincter of Oddi inhibited the spontaneous contractile activity and lowered base-line tension considerably. A contraction usually followed the period of stimulation. 2 These inhibitory effects were prevented by tetrodotoxin 0.1-0.5 mug/ml but were not reduced by hexamethonilm, morphine, or blockade of alpha- or beta-adrenoreceptors of cholinoceptors with phenoxy-benzamine propranolol or atropine, respectively. 3 Adenosine-5'-triphosphate (ATP) and adenosine-5'-diphosphate (ADP) inhibited the spontaneous sphincter activity and caused relaxation thus mimicking the effects of the C-terminal octapeptide of cholecystokinin (C8-CCK), isoprenaline and prostaglandin E1 and E2. 4 ATP alone (greater than 100 mug/ml) or ATP (greater than 10 mug/ml) plus dipyridamole (1 mug/ml), relaxed the sphincter to the same degrees as did the field stimulation. 5 In sphincter maximally contracted by acetylcholine, the effect of stimulation was more marked than that recorded in uncontracted preparations. 6 The present findings suggest that the sphincter of Oddi receives inhibitory nerves that are neither cholinergic nor adrenergic.

Acetylcholine↗

Mechanical and metabolic effects of beta-receptor stimulators, the C-terminal octapeptide of cholecystokinin, and prostaglandin E2 on the isolated, depolarized sphincter of Oddi.

Similar to their actions on normally polarized, isolated sphincter of Oddi, the beta-receptor stimulators isoprenaline and tebutaline, and prostaglandin E2 produced relaxation of the depolarized preparation. The relaxation was accompained by an increase in the intracellular content of cyclic AMP. In contrast to its relaxing effect on normally polarized sphincter preparations, the C-terminal octapeptide of cholecystokinin (C8-CCK) contracted or had no effect on the depolarized sphincter. There was no change or a small decrease in the content of cyclic AMP in the muscle. It is suggested that the relaxing effects of beta-receptor stimulators and prostaglandin E2 on isolated sphinceter of Oddi, and the simultaneous increase in cyclic AMP-content are mediated processes independent of the electrical acitivty of the membrane. However, C8-CCK mediated relaxation and increase in cyclic AMP is dependent on the membrane potential.

Ampulla of Vater↗

Effects of terbutaline on human uterine motility at term.

The effects of the selective beta-2-receptor stimulator terbutaline on the activity of gravid, human myometrium were investigated in vitro and in vivo, before and after administration of different beta-receptor blockers. Terbutaline, 0.2-1.0 mu-g/ml, inhibited the spontaneous contractile activity of isolated strips of myometrium. This effect was unaffected by the selective beta-a-receptor blockers practolol, 1 mu-g/ml, and H 93/26, 1 mu-g/ml. However, the non-selective blocker propranolol, 0.1 mu-g/ml, completely inhibited the terbutaline effects. The in vitro effects of terbutaline could be correlated with findings in vivo. Intra-uterine pressure was recorded in 4 pregnant women at term. Infusion of terbutaline, 10-15 mu-g/min, for 20-40 min, effectively inhibited both spontaneous and oxytocin-stimulated uterine activity. There was a moderate increase in maternal heart rate, but no consistent effect on maternal blood pressure. Fetal heart rate was little affected. The uterine effects of terbuline were not influenced by practolol, 5-20 mg i.v., but completely inhibited by propranolol, 1-2 mg i.v. The results suggest that terbutaline inhibits uterine motility by effects on uterine beta-2-receptors and that it can be given in clinically effective doses without adverse circulatory effects on mother or fetus.

Adult↗