ABSTRACT
To study the changes in every part of the β-adrenergic signal transduction pathway and their effects on ischemic preconditioning of rat myocardium in vivo. SD rats were divided into three groups: IP group, I/R group and CON group. The IP group was further divided into PC1-, 2-,3-, and PC1+, 2+, 3+ groups according to preconditioning procedure. The rats received surgical procedure and underwent left coronary artery occlusion and reperfusion. We analyzed the infarct size by TTC staining, measured serum myocardial enzymes, studied the β-AR Bmax and Kd by radioligand binding assay of receptors, checked the activity of AC and PKA by the method of biochemistry and examined the content of cAMP by radioimmunoassay. The infarct area was much smaller in the IP group than in the I/R group (P＜0. 001), while the enzymes were significantly higher in I/R (P＜0. 001). The Bmax of β-AR in IP was much higher than that in I/R (P＜0.001), but no difference in Kd could be seen between IP and I/R groups. In IP, the activity of AC and PKA and the content of cAMP were higher than those in I/R (P＜0.05, 0. 002 and 0. 001, respectively). In the procedure of preconditioning, the content of cAMP and the activity of PKA showed the characteristic of cyclic fluctuation. Ischemic preconditioning can protect the heart from necrosis and reduce endo-enzyme leakage. The system of β-adrenergic signal transduction pathway probably takes part in the protection effect of the IP, which might be elicited by the PKA .
ABSTRACT
AIM: The role of cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) in the induction and maintenance of spinal long-term potentiation (LTP) was evaluated. METHODS: The C-fiber evoked field potentials were recorded at the superficial layers of spinal dorsal horn at the lumbar enlargement. RESULTS: (1) 8-Br-cAMP induced LTP of C-fiber evoked field potentials and 8-Br-cAMP-induced LTP occludes tetanus-induced LTP. (2) Rp-CPT-cAMPS, an inhibitor of PKA, blocked the induction of spinal LTP and reversed established LTP of C-fiber evoked field potentials in a time-dependent manner. (3) In the presence of anisomycin, a protein synthesis inhibitor, the potentiation induced by 8-Br-cAMP was completely blocked. (4) PD98059, a selective inhibitor of mitogen-activated protein kinase (MAPK),completely blocked the 8-Br-cAMP-induced LTP.CONCLUSION: Activation of PKA signal pathway in spinal dorsal horn may be crucial for the induction and the early-phase maintenance of LTP of C-fiber evoked field potentials.