Muscarinic M positive allosteric modulator ASP8302 enhances bladder contraction and improves voiding dysfunction in rats.

Objectives: Muscarinic M (M ) receptors mediate cholinergic smooth muscle contraction of the bladder. Current drugs targeting bladder M receptors for micturition disorders have a risk of cholinergic side effects due to excessive receptor activation and insufficient selectivity. We investigated the effect of ASP8302, a novel positive allosteric modulator (PAM) of M receptors, on bladder function in rats.

Potentiation of Muscarinic M Receptor Activation through a New Allosteric Site with a Novel Positive Allosteric Modulator ASP8302.

Muscarinic M (M) receptors mediate a wide range of acetylcholine (ACh)-induced functions, including visceral smooth-muscle contraction and glandular secretion. Positive allosteric modulators (PAMs) can avoid various side effects of muscarinic agonists with their spatiotemporal receptor activation control and potentially better subtype selectivity. However, the mechanism of allosteric modulation of M receptors is not fully understood, presumably because of the lack of a potent and selective PAM.

Urinary metabolites identified using metabolomic analysis as potential biomarkers of nocturia in elderly men.

Purpose: To investigate the association between nocturia and urinary metabolites in elderly men using metabolomic analysis.

Methods: We recruited 66 men aged 65-80 years. The 3-day frequency volume chart (FCV), International Prostate Symptom Score (IPSS), and quality of life score were used to assess micturition behavior.

Effect of ASP2205 fumarate, a novel 5-HT receptor agonist, on urethral closure function in rats.

The pharmacological profile of ASP2205 fumarate (ASP2205), a novel 5-HT receptor agonist, was evaluated in vitro and in vivo. ASP2205 showed potent and selective agonistic activity for the human 5-HT receptor, with an EC of 0.85 nM in the intracellular Ca mobilization assay.

Liquid chromatography-mass spectrometry identification of serum biomarkers for nocturia in aged men.

Purpose: We aimed to investigate the association between nocturia and serum metabolites identified using metabolomics analysis.

Methods: This study enrolled 66 men aged 65-80 years, recruited from the outpatient department of a university hospital. The participants were stratified as follows: Nocturia group [45 men with any total international prostate symptom score (IPSS) and an average of 3 nights ≥ 1.

Effect of Selective Prostaglandin E2 EP2 Receptor Agonist CP-533,536 on Voiding Efficiency in Rats with Midodrine-Induced Functional Urethral Obstruction.

Objectives: We investigated the effect of the selective prostaglandin E2 EP2 receptor agonist CP-533,536 on voiding efficiency in rats with midodrine-induced functional urethral obstruction.

Methods: The effect of CP-533,536 (0.03-0.

Study on Physiological Roles of Stimulation of Prostaglandin E2 Receptor Subtype EP2 in Urethral Function in Rats.

Objectives: We investigated the relaxant effect of stimulation of prostaglandin E2 (PGE2 ) receptor subtype EP2 as well as the involvement of a cyclic AMP (cAMP)-dependent pathway related to stimulation of EP2 receptors in urethral function in rats by evaluating effects of PGE2 and selective EP2 receptor agonist CP-533,536.

Methods: Effects of PGE2 and CP-533,536 on cAMP accumulation were assessed in Chinese hamster ovary (CHO)-K1 cells expressing rat EP2 or EP4 receptors. Relaxant responses to PGE2 and CP-533,536 (0.

Effect of YM-254890, a specific Galphaq/11 inhibitor, on experimental peripheral arterial disease in rats.

The protective effect of YM-254890, a specific Galphaq/11 inhibitor, on laurate-induced peripheral arterial disease in rats was compared with those of prostaglandin E1 (PGE1), beraprost, and clopidogrel. YM-254890 inhibited ADP-induced ex vivo rat platelet aggregation at a dose of 3 microg/kg. Furthermore, YM-254890 strongly inhibited phenylephrine-, serotonin- and endothelin-1-induced contractions in the rat aorta, and improved dermal blood flow after the laurate injection.

Pharmacological properties of YM-254890, a specific G(alpha)q/11 inhibitor, on thrombosis and neointima formation in mice.

The pharmacological properties of YM-254890, a specific G(alpha)q/11 inhibitor, on acute thrombosis and chronic neointima formation after vascular injury have been investigated. FeCl3 was used to induce vascular injury in the carotid artery of mice. For the thrombosis studies, the test drug was either intravenously or orally administered before vascular injury.

L-type Ca2+ channels serve as a sensor of the SR Ca2+ for tuning the efficacy of Ca2+-induced Ca2+ release in rat ventricular myocytes.

In cardiac excitation-contraction coupling, Ca2+-induced Ca2+ release (CICR) from ryanodine receptors (RyRs), triggered by Ca2+ entry through the nearby L-type Ca2+ channel, induces Ca2+-dependent inactivation (CDI) of the Ca2+ channel. Aiming at elucidating the physiological role of CDI produced by CICR (CICR-dependent CDI), we investigated the contribution of the CICR-dependent CDI to action potential (AP) waveform and the amount of Ca2+-influx through Ca2+ channels during AP in rat ventricular myocytes. The elimination of the CICR-dependent CDI, by depletion of the SR Ca2+ with thapsigargin, significantly prolonged AP duration (APD).