Figure 5: α1A-AR Activation of ERK in Human Heart Slices

After 1 day in culture, duplicate left ventricular myocardial slices were treated for 15 min with varying doses of the alpha-1A-adrenergic receptor (α1A-AR) agonist A61603 (A6). ERK dually phosphorylated at Thr202 and Tyr204 of Erk1 (Thr185 and Tyr187 of Erk2) was measured by immunoblot. (A) pERK immunoblot with varying A61603 doses in a nonfailing slice; a Coomassie-stained gel and a blot of total ERK (tERK) show equal loading. (B) Concentration-response relationships for total pERK in the indicated number of failing and nonfailing hearts, with duplicate slices for each heart at each dose; mean ± SE. Emax values for both failing and nonfailing are different from 1.0 (p < 0.05 by confidence limits). Failing and nonfailing Emax and EC50 do not differ by curve fitting. Three failing patients were treated with a left ventricular assist device, and 1 with carvedilol. (C) pERK immunohistochemistry in failing slices shows pERK in interstitial cells (ISCs) with both vehicle and A61603, and diffusely increased pERK in myocyte cytoplasm with A61603 1 μmol/l 15 min (e.g., asterisks). Abbreviations as in Figure 5.



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