Effects of β-blockers on house dust mite-driven murine models pre- and post-development of an asthma phenotype.

Background: Our previous studies suggested certain β-adrenoceptor blockers (β-blockers) attenuate the asthma phenotype in ovalbumin driven murine models of asthma. However, the ovalbumin model has been criticized for lack of clinical relevance.

Methods: We tested the non-selective β-blockers, carvedilol and nadolol, in house dust mite (HDM) driven murine asthma models where drugs were administered both pre- and post-development of the asthma phenotype.

Differential effects of inescapable stress on locus coeruleus GRK3, alpha2-adrenoceptor and CRF1 receptor levels in learned helpless and non-helpless rats: a potential link to stress resilience.

Exposure of rats to unpredictable, inescapable stress results in two distinct behaviors during subsequent escape testing. One behavior, suggestive of lack of stress resilience, is prolonged escape latency compared to non-stressed rats and is labeled learned helplessness (LH). The other behavior suggestive of stress resilience is normal escape latency and is labeled non-helpless (NH).

Chronic adrenaline treatment fails to down-regulate the Del301-303-alpha2B-adrenoceptor in neuronal cells.

Background And Purpose: A polymorphism of the human alpha(2B)-adrenoceptor (Del(301-303)-alpha(2B)-adrenoceptor) has been described, and this receptor exhibits reduced G-protein-coupled receptor kinase (GRK) phosphorylation and impaired short-term desensitization. Expression of the Del(301-303)-alpha(2B)-adrenoceptor also is associated with an increased risk for myocardial infarction in humans. Recent evidence from our laboratory suggests a quantitative relationship between cellular GRK3 expression levels and the sensitivity of the alpha(2B)-adrenoceptor to agonist-induced down-regulation.

The presence of beta2-adrenoceptors sensitizes alpha2A-adrenoceptors to desensitization after chronic epinephrine treatment.

Background: In addition to the regulation of blood pressure, alpha2- and beta-adrenoceptor (AR) subtypes play an important role in the modulation of noradrenergic neurotransmission in the human CNS and PNS. Several studies suggest that the alpha2-AR responsiveness in cells and tissues after chronic epinephrine (EPI) or norepinephrine (NE) exposure may vary, depending on the beta-AR activity present there. Recently, we reported that in BE(2)-C human neuroblastoma cells (endogenously expressing alpha2A- and beta2-AR), chronic EPI treatment (300 nM) produced a dramatic beta-adrenoceptor-dependent desensitization of the alpha2A-AR response.

Activation of the CRF(1) receptor causes ERK1/2 mediated increase in GRK3 expression in CATH.a cells.

G-protein coupled receptor kinase 3 (GRK3) mediates desensitization of alpha(2)-adrenergic (alpha(2)-AR) and CRF(1) receptors. CRF(1) receptors, alpha(2)-AR and GRK3, are localized to the primary source of noradrenergic inputs to higher brain centers critical in both the response to stress and the development of depression, namely, locus coeruleus (LC). This study utilizing CATH.