Relaxation of airway smooth muscle (ASM) by beta-adrenoceptor agonists involves reduction of intracellular Ca2+ concentration ([Ca2+]i). In porcine ASM cells, acetylcholine induces [Ca2+]i oscillations that display frequency modulation by agonist concentration and basal [Ca2+]i. We used real-time confocal microscopy to examine the effect of salbutamol (1 nM to 1 microM), a beta 2-adrenoceptor a...

Recent studies indicate that norepinephrine-induced contractile oscillations in the tail artery from stroke-prone spontaneously hypertensive rats (SHRSP) may be a vascular phenomenon independent of blood pressure level. The objectives of this study were: (1) to characterize pharmacologically the alpha-adrenoceptor mediating norepinephrine-induced oscillations in tail artery; and (2) to investig...

PURPOSE Patients treated with propranolol, a nonselective β-adrenoceptor antagonist, develop severe anaphylaxis, but the mechanism remains unknown. We determined effects of β₁- and β₂-adrenoceptor antagonists on the anaphylaxis-induced increase in vascular permeability in mice. METHODS In anesthetized ovalbumin-sensitized C57BL mice, mean arterial blood pressure (MBP) was measured, and Evans ...

Compared with epinephrine, the relative intrinsic activity of a series of partial agonists to activate fusion proteins between the porcine alpha-2A adrenoceptor and the a-subunit of Gi1 was reduced after a single-point mutation (CysGly) in the G protein. Although UK14304 was close to a full agonist at the fusion construct containing wild-type (Cys)Gi1a, it was a partial agonist at that containi...

Previous in vitro work on rabbit knee joint vessels showed that vasoconstrictor effects of nerve stimulation and administration of α-adrenoceptor agonists were mediated predominantly by α1-adrenoceptors5,9 The present experiments were performed to assess the nature of α-adrenoceptor subtypes within these blood vessels in vivo. Dose/response relationships for adrenaline and noradrenaline pr...

previous in vitro work on rabbit knee joint vessels showed that vasoconstrictor effects of nerve stimulation and administration of α-adrenoceptor agonists were mediated predominantly by α1-adrenoceptors5,9 the present experiments were performed to assess the nature of α-adrenoceptor subtypes within these blood vessels in vivo. dose/response relationships for adrenaline and noradrenaline produce...

Rhinovirus (RV) infections account for approximately two thirds of all virus-induced asthma exacerbations and often result in an impaired response to β2 agonist therapy. Using an in vitro model of RV infection, we investigated the mechanisms underlying RV-induced β2 adrenoceptor desensitization in primary human airway smooth muscle cells (ASMC). RV infection of primary human bronchial epithelia...

The important regulator of cardiac function, cAMP, is hydrolyzed by different cyclic nucleotide phosphodiesterases (PDEs), whose expression and activity are not uniform throughout the heart. Of these enzymes, PDE2 shapes β1 adrenoceptor-dependent cardiac cAMP signaling, both in the right and left ventricular myocardium, but its role in regulating β2 adrenoceptor-mediated responses is less well ...

The preclinical pharmacological profile of indacaterol, a novel, chirally pure inhaled beta(2) adrenoceptor agonist, is described in this chapter. In various in vitro systems, indacaterol is close to a full agonist at the human β2-adrenoceptor with nanomolar potency. In isolated superfused human and guinea pig trachea, indacaterol has a fast onset of and a long duration of action. In the consci...

BACKGROUND Alterations in brain density and signaling associated with monoamine receptors are believed to play a role in depressive disorders. This study evaluates the functional status of α₂(A)-adrenoceptors in postmortem frontal cortex of depressed subjects. METHODS G-protein activation and inhibition of adenylyl cyclase (AC) activity induced by the α₂-adrenoceptor agonist UK14304 were meas...