Functional characterization of beta-adrenoceptor subtypes in the canine and rat lower urinary tract.

Purpose: We compared the effect of a beta 3-adrenoceptor (AR) agonist with that of beta 1 and beta 2-AR agonists on the urethra and bladder in the dog and rat.

Materials And Methods: In an in vitro experiment we studied the relaxant effect of subtype selective beta-AR agonists in canine and rat urethral and bladder smooth muscle using an organ bath method. In addition, in urethane anesthetized rats we measured urethral pressure and bladder pressure simultaneously in the presence of the beta 3-agonist CL316243 and the beta 2-agonist procaterol in 4 or 5 animals.

Effects of beta(3)-adrenoceptor stimulation on prostaglandin E(2)-induced bladder hyperactivity and on the cardiovascular system in conscious rats.

Aims: To investigate the effects of selective beta(2)- and selective beta(3)-adrenoceptor (AR) agonists on prostaglandin (PG) E(2)-induced bladder hyperactivity in conscious free-moving rats.

Methods: Female Sprague-Dawley rats were anesthetized for implantation of bladder, intravenous, and intra-arterial catheters. The effects of a beta(3)-AR agonist (CL316,243) on cystometric and cardiovascular parameters were assessed in conscious rats.

Effects of selective beta2 and beta3-adrenoceptor agonists on detrusor hyperreflexia in conscious cerebral infarcted rats.

Purpose: We evaluated the effects of beta-adrenoceptor agonists on detrusor hyperreflexia in cerebral infarcted rats.

Materials And Methods: To produce cerebral infarction in Sprague-Dawley rats the left middle cerebral artery was occluded by introducing a monofilament nylon thread into the artery. In sham operated rats the same artery was exposed but not occluded.

KDR-5169, a new gastrointestinal prokinetic agent, enhances gastric contractile and emptying activities in dogs and rats.

KDR-5169, 4-amino-5-chloro-N-[1-(3-fluoro-4-methoxybenzyl)piperidin-4-yl]-2-(2-hydroxyethoxy)benzamide hydrochloride dihydrate, is a new prokinetic with a dual action, i.e., stimulation of the 5-HT4 receptor and antagonism of the dopamine D2 receptor.

Effects of dopamine d2 receptor agonists in a pituitary transplantation-induced hyperprolactinaemia/anovulation model in rats.

1. In the present study, we investigated the effects of hyperprolactinaemia, induced by transplantation of anterior pituitary glands under the kidney capsule in female rats, on the relationship between serum and pituitary concentrations of the gonadotropins and on the oestrous cycle. 2.

Discovery of novel N-phenylglycine derivatives as potent and selective beta(3)-adrenoceptor agonists for the treatment of frequent urination and urinary incontinence.

With a novel assay using isolated ferret detrusor to estimate beta(3)-adrenoceptor agonistic activity, we found that a series of glycine derivatives of ritodrine, a beta(2)-adrenoceptor agonist, are potent beta(3)-adrenoceptor agonists, with excellent selectivity versus beta(1) and beta(2) subtypes. Substitution of halogens in the phenyl ring increased potency and selectivity for the beta(3)-adrenoceptor, and this was dependent upon the position of the halogens. The chlorine-substituted derivatives 3f-i exhibited potent beta(3)-adrenoceptor-mediated relaxation of ferret detrusor (EC(50) = 0.

Study of low molecular weight heparin effect on the relation between anticoagulant activity and antithrombin III affinity.

Low molecular weight heparin (FR-860), and conventional unfractionated heparin (UF-heparin) were fractionated by rabbit antithrombin III (AT III)-Sepharose, and the effects of each affinity fraction on the coagulation and fibrinolytic activities were investigated. FR-860 was fractionated to no-affinity, low-affinity (LA) and high-affinity (HA) fractions, and UF-heparin to LA and HA fractions. The HA fractions showed higher activities regarding the prolongation of activated partial thromboplastin time, anti-factor Xa activity and antithrombin activity compared with those of LA.

Study of anticoagulant mechanism of low molecular weight heparin.

The binding ability of low molecular weight heparin (FR-860), and conventional unfractionated heparin (UF-heparin) to factor Xa (F.Xa), thrombin and AT III was investigated using FR-860- and UF-heparin-Sepharoses. FR-860 could not bind directly to F.

[Effects of low molecular weight heparin (FR-860) on the experimental disseminated intravascular coagulation models].

Effects of low molecular weight heparin (FR-860) on experimental disseminated intravascular coagulation (DIC) models in rats were compared with those of conventional unfractionated heparin (UF-heparin) and other anticoagulants. In the endotoxin-induced DIC model, FR-860 (12.5-200 U/kg/hr) and UF-heparin (25-200 U/kg/hr) inhibited dose-dependently the decreases in platelet counts, fibrinogen, antithrombin III activity and alpha 2-plasmin inhibitor activity, and they also inhibited the increases in fibrin de-products and thrombus formation in the glomerular capillary bed.