Object We aimed to identify the β-adrenoceptor (β-AR) subtypes involved in isoprenaline-induced relaxation of guinea pig colonic longitudinal smooth muscle using pharmacological and biochemical approaches. Methods Longitudinal smooth muscle was prepared from the male guinea pig ascending colon and contracted with histamine prior to comparing the relaxant responses to three catecholamines (isoprenaline, adrenaline, and noradrenaline). The inhibitory effects of subtype-selective β-AR antagonists on isoprenaline-induced relaxation were then investigated. Results The relaxant potencies of the catecholamines were ranked as: isoprenaline > noradrenaline ≈ adrenaline, whereas the rank order was isoprenaline > noradrenaline > adrenaline in the presence of propranolol (a non-selective β-AR antagonist; 3 × 10⁻⁷ M). Atenolol (a selective β₁-AR antagonist; 3 × 10⁻⁷–10⁻⁶ M) acted as a competitive antagonist of isoprenaline-induced relaxation, and the pA₂ value was calculated to be 6.49 (95% confidence interval: 6.34–6.83). The relaxation to isoprenaline was not affected by ICI-118,551 (a selective β₂-AR antagonist) at 10⁻⁹–10⁻⁸ M, but was competitively antagonized by 10⁻⁷–3 × 10⁻⁷ M, with a pA₂ value of 7.41 (95% confidence interval: 7.18–8.02). In the presence of propranolol (3 × 10⁻⁷ M), the relaxant effect of isoprenaline was competitively antagonized by bupranolol (a non-selective β-AR antagonist), with a pA₂ value of 5.90 (95% confidence interval: 5.73–6.35). Conclusion These findings indicated that the β-AR subtypes involved in isoprenaline-induced relaxation of colonic longitudinal guinea pig muscles are β₁-AR and β₃-AR.

Object We identified the β-adrenoceptor (β-AR) subtypes responsible for the relaxant responses to adrenaline (AD) and noradrenaline (NA) in the rat thoracic aorta and examined the role of cAMP which is involved in these relaxant responses. Methods The effects of β-AR antagonists or the adenylyl cyclase inhibitor SQ 22,536 on AD- and NA-induced relaxant responses in phenylephrine-induced contraction and increases in cAMP levels were examined in isolated, endothelium-denuded rat thoracic aorta segments. Results AD-induced relaxation was completely suppressed by propranolol (10⁻⁷ M) or by ICI-118,551 (10⁻⁸ M) plus atenolol (10⁻⁶ M), and was also very strongly inhibited by ICI-118,551 (10⁻⁸ M) alone. AD (10⁻⁵ M) increased tissue cAMP levels by approximately 1.9-fold compared with that in non-stimulated aortic tissue, but did not significantly increase cAMP levels in the presence of ICI-118,551 (10⁻⁸ M) or SQ 22,536 (10⁻⁴ M). AD-induced relaxation was strongly suppressed by SQ 22,536 (10⁻⁴ M). NA-induced relaxation was almost completely suppressed by atenolol (10⁻⁶ M) plus ICI-118,551 (10⁻⁸ M) although it was hardly affected by ICI-118,551 (10⁻⁸ M) alone. NA (10⁻⁵ M) increased tissue cAMP levels by approximately 2.2-fold compared with that in non-stimulated aortic tissue, but did not significantly increase cAMP levels in the presence of atenolol (10⁻⁶ M) or SQ 22,536 (10⁻⁴ M). NA-induced relaxation was strongly suppressed by SQ 22,536 (10⁻⁴ M). Conclusion In rat thoracic aorta, AD- and NA-induced relaxations, which are both strongly dependent on increased tissue cAMP levels, are mainly mediated through β₂- and β₁-adrenoceptors respectively.

A hallmark of smooth muscle cells is their ability to adapt their functions to meet temporal and chronic fluctuations in their demands. These functions include force development and growth. Understanding the mechanisms underlying the functional plasticity of smooth muscles, the major constituent of organ walls, is fundamental to elucidating pathophysiological rationales of failures of organ functions. Also, the knowledge is expected to facilitate devising innovative strategies that more precisely monitor and normalize organ functions by targeting individual smooth muscles. Evidence has established a current paradigm that the myosin light chain phosphatase (MLCP) is a master regulator of smooth muscle responsiveness to stimuli. Cellular MLCP activity is negatively and positively regulated in response to G-protein activation and cAMP/cGMP production, respectively, through the MYPT1 regulatory subunit and an endogenous inhibitor protein named CPI-17. In this article we review the outcomes from two decade of research on the CPI-17 signaling and discuss emerging paradoxes in the view of signaling pathways regulating smooth muscle functions through MLCP.

The prostate is a gland whose secretions contribute to the seminal fluids ejaculated upon activation of autonomic sympathetic nerves. In elder males, the prostate undergoes an increase in stroma mass and myogenic tone, leading to benign prostatic hyperplasia that occludes the proximal urethra and the presentation of various lower urinary tract symptoms that decrease their quality of life. This review summarises the role of prostatic interstitial cells (PICs) in the generation of the spontaneous tone in the prostate. It presents current knowledge of the role of Ca²⁺ plays in PIC pacemaking, as well as the mechanisms by which this spontaneous activity triggers slow wave generation and stromal contraction. PICs display a small T-type Ca²⁺ current (I_CaT) and a large L-type Ca²⁺ current (I_CaL). In contrast to other interstitial cells in the urinary and gastrointestinal tracts, spontaneous Ca²⁺ signalling in PICs is uniquely dependent on Ca²⁺ influx through I_CaL channels. A model of prostatic pacemaking is presented describing how I_CaL can be triggered by an initial membrane depolarization evoked upon the selective opening of Ca²⁺-activated Cl^– channels by Ca²⁺ flowing only through I_CaT channels. The resulting current flow through I_CaL results in release of Ca²⁺ from internal stores and the summation of Cl^–-selective spontaneous transient depolarizations (STDs) to form pacemaker potentials that propagate passively into the prostatic stroma to evoke regenerative action potentials and excitation-contraction coupling.