TriCat Research ELISA Kit

Background: The release of catecholamines is preceded by glucocorticoids during a stress response. We have shown that ozone-induced pulmonary responses are mediated through the activation of stress hormone receptors. Objective: To examine the interdependence of beta-adrenergic (beta AR) and glucocorticoid receptors (GRs), we inhibited beta AR while inducing GR or inhibited GR while inducing beta AR and examined ozone-induced stress response. Methods: Twelve-week-old male Wistar-Kyoto rats were pretreated daily with saline or propranolol (PROP; beta AR-antagonist; 10 mg/kg-i.p.; starting 7-d prior to exposure) followed-by saline or dexamethasone (DEX) sulfate (GR-agonist; 0.02 mg/kg-i.p.; starting 1-d prior to exposure) and exposed to air or 0.8 ppm ozone (4 h/d x 2-d). In a second experiment, rats were similarly pretreated with corn-oil or mifepristone (MIFE; GR-antagonist, 30 mg/kg-s.c.) followed by saline or clenbuterol (CLEN; beta(2)AR-agonist; 0.02 mg/kg-i.p.) and exposed. Results: DEX and PROP + DEX decreased adrenal, spleen and thymus weights in all rats. DEX and MIFE decreased and increased corticosterone, respectively. Ozone-induced pulmonary protein leakage, inflammation and IL-6 increases were inhibited by PROP or PROP + DEX and exacerbated by CLEN or CLEN + MIFE. DEX and ozone-induced while MIFE reversed lymphopenia (MIFE > CLEN + MIFE). DEX exacerbated while PROP, MIFE, or CLEN + MIFE inhibited ozone-induced hyperglycemia and glucose intolerance. Ozone inhibited glucose-mediated insulin release. Conclusions: In summary, 1) activating beta AR, even with GR inhibition, exacerbated and inhibiting beta AR, even with GR activation, attenuated ozone-induced pulmonary effects; and 2) activating GR exacerbated ozone systemic effects, but with beta AR inhibition, this exacerbation was less remarkable. These data suggest the independent roles of beta AR in pulmonary and dependent roles of beta AR and GR in systemic effects of ozone.

The role of catecholamine receptors in cardiac energy metabolism is unknown. alpha(1)-adrenergic receptors (alpha(1)-ARs) have been identified to play a role in whole body metabolism but its role in cardiac energy metabolism has not been explored. We used freshly prepared primary adult mouse cardiomyocytes and incubated with either(14)C-palmitate or(14)C-glucose tracers to measure oxidation rates in the presence or absence of phenylephrine, an alpha(1)-AR agonist (with beta and alpha(2)-AR blockers) under normal cell culture conditions.(14)CO(2)released was collected over a 10 min period in covered tissue culture plates using a 1 M hyamine hydroxide solution placed in well cups, counted by scintillation and converted into nmoles/hr. We found that phenylephrine stimulated glucose oxidation but not fatty acid oxidation in adult primary cardiomyocytes. alpha(1)-AR stimulated glucose oxidation was blocked by the AMPK inhibitor, dorsomorphin dihydrochloride, and the PKC inhibitor, rottlerin. Ischemic conditions were induced by lowering the glucose concentration from 22.5 mM to 1.375 mM. Under ischemic conditions, we found that phenylephrine also increased glucose oxidation. We report a direct role of alpha(1)-ARs in regulating glucose oxidation under normal and ischemic conditions that may lead to new therapeutic approaches in treating ischemia.