The authors describe the scientific rationale for using an inhaled corticosteroid with an inhaled long-acting beta 2-agonist. They discuss the clinical trials demonstrating that using an inhaled corticosteroid with an inhaled long-acting beta 2-agonist provides greater overall asthma control compared with increasing the dose of inhaled corticosteroid. In addition, they review the clinical trial...

BACKGROUND Sustained agonist-promoted ubiquitination of beta-arrestin has been correlated with increased stability of the GPCR - beta-arrestin complex. Moreover, abrogation of beta-arrestin ubiquitination has been reported to inhibit receptor internalization with minimal effects on receptor degradation. RESULTS Herein we report that agonist activation of M1 mAChRs produces a sustained beta-ar...

Sustained stimulation of several G protein-coupled receptors is known to lead to a reduction in the signaling efficacy. This phenomenon, named agonist-induced desensitization, has been best studied for the beta 2-adrenergic receptor (AR) and is characterized by a decreased efficacy of beta-adrenergic agonists to stimulate the adenylyl cyclase activity. Recently, several beta-adrenergic ligands ...

Multiple and paradoxical effects of airway smooth muscle (ASM) 7-transmembrane-spanning receptors activated during asthma, or by treatment with bronchodilators such as beta(2)-adrenergic receptor (beta(2)AR) agonists, indicate extensive receptor crosstalk. We examined the signaling of the prostanoid-EP(1) receptor, since its endogenous agonist prostaglandin E(2) is abundant in the airway, but i...

Primary adipocytes were isolated from axillary brown adipose tissue from adult cynomolgus monkeys. That this tissue contained brown adipocytes was verified by morphological examination and by demonstrating the presence of uncoupling protein messenger ribonucleic acid in the isolated adipocytes. The contributions of beta 1-, beta 2-, and beta 3-adrenergic receptors (AR) to lipolysis and oxygen c...

Neurotensin receptor activation augments the biosctivity of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). JMV-449, a C-terminal neurotensin-like fragment with reduced peptide bond, represents neurotensin agonist. The present study assessed actions JMV-449 on pancreatic beta-cells alone, in combination GIP GLP-1. Further studies examined impact incretin ...

A significant minority of patients with COPD have favorable response to corticosteroid treatment. In addition, the benefit of corticosteroid treatment may be outweighed by the side effects. Long-term administration of inhaled steroids is a safe means of treatment. We hypothesized that treatment with high-dose inhaled budesonide would improve clinical symptoms and pulmonary function in subjects ...