Mats Elmér

Inhibitory β-adrenoceptors in the urinary bladder of the rat

Abstract The β-adrenoceptors of the urinary bladder were investigated in the rat in vivo . Isoprenaline, and the β2-stimulating agents terbutaline and salbutamol elicited relaxation of the detrusor muscle decreasing the intravesical pressure. The responses were not affected by the β1-blocking agents practolol or H 93/26 but were totally abolished by propranolol and the β2-blocking agent H 35 25 . Noradrenaline given after dihydro-ergotamine caused relaxation of the detrusor muscle and this response was completely blocked by propranolol and H 35 25 . It is concluded that the β-adrenoceptors of the rat urinary bladder belong to the type of inhibitory receptors classified as β2-receptors in other organs.

Innervation of the Child Urinary Bladder

Muscle strips from the fundus, trigonum and distal ureters obtained from children at operations for vesico-ureteric reflux were studied using histochemical and immunohistochemical methods, and electrical nerve stimulation in an organ bath. A rich supply of cholinergic nerves was found and despite a partial atropine resistance the neurophysiological experiments indicated that the transmitter causing contraction of the detrusor muscle is acetylcholine. Imipramine, which is used in the treatment of enuresis, had no anticholinergic effect on the bladder in the doses used clinically. The adrenergic innervation was very sparse except around the ureter orifices. No contractile alpha-adrenoceptors could be detected but beta receptor mediated relaxation was found, which was neither of the beta 1 nor beta 2 type. A third type of beta receptor is postulated. Peptidergic nerves containing vasoactive intestinal peptide, VIP, were demonstrated in a few nerve terminals running along bundles of smooth muscle. No nerves containing enkephaline, somatostatine or substance P were found. VIP affected the detrusor muscle indicating a possible role as a modulator of transmitter action, while substance P had no effect. The anticholinergic and calcium antagonistic drug terodiline inhibited all muscle activity, whether it was induced by nerve stimulation, cholinergic drugs or a potassium rich solution, making it suitable for treatment of diurnal enuresis.

Urinary bladder innervation in children.

Muscle strips from the fundus, trigone, and distal ureter obtained from children at operation for vesicoureteric reflux were studied using histochemical and immunohistochemical methods, and electrical nerve stimulation in an organ bath. A rich supply of cholinergic nerves was found and the transmitter causing contraction of the detrusor muscle was regarded as being acetylcholine. The adrenergic innervation was very sparse except around the ureteric orifices. No contractile alpha-adrenoceptors could be detected but beta-receptor-mediated relaxation was found. The type was not beta 1 or beta 2, suggesting a third type of beta-receptor. Peptidergic nerves containing vasoactive intestinal peptide (VIP) were demonstrated in a few nerve terminals. No nerves containing enkephalin, somatostatin, or substance P were found. VIP affected the detrusor muscle, indicating a possible role as a modulator of transmitter action. Imipramine, used for enuresis, had no anticholinergic effect on the bladder in the doses used clinically. The anticholinergic and calcium antagonistic drug terodiline inhibited all muscle activity, making it suitable for treatment of diurnal enuresis.

Supersensitivity in the Isolated Urethra of the Rat Following “Chemical Sympathectomy”

The circular muscle activity of the urethra of the male rat was isometrically measured in vitro in response to noradrenaline, phenylephrine and isoprenaline. The urethra was found to be supplied with both alpha- and beta-adrenoceptors mediating contraction and relaxation, respectively. The substance 6-hydroxydopamine is known to cause a selective destruction of adrenergic nerves. In the present study 6-hydroxydopamine (100 mg/kg) was injected intravenously into a group of rats twice with a weekly interval. When the urethra was examined 2-3 weeks after the first injection a supersensitivity mediated both via alpha- and beta-adrenoceptors was found to have developed, suggesting that the urethra of the male rat normally is under the influence of adrenergic activity. The findings are discussed in relation to denervation supersensitivity of the neurogenic bladder in man.