Influence of phosphodiesterases and cGMP on cAMP generation and on phosphorylation of phospholamban and troponin I by 5-HT4 receptor activation in porcine left atrium.

摘要: Our objective was to investigate the role of phosphodiesterase (PDE)3 and PDE4 cGMP in control cAMP metabolism phosphorylation troponin I (TnI) phospholamban (PLB) when 5-HT4 receptors are activated pig left atrium. Electrically paced porcine atrial muscles, mounted organ baths, received stimulators particulate guanylyl cyclase (pGC) or soluble (sGC) and/or specific PDE inhibitors followed by 5-HT receptor agonist prucalopride. Muscles were freeze-clamped at different moments exposure measure cAMP/protein kinase A targets TnI PLB immunoblotting levels enzyme immunoassay. Corresponding with functional results, only transiently increased content, but caused a less quickly declining did not significantly change phosphorylation. Under combined PDE3 inhibition, 5-HT-induced increase enhanced sustained, now also increased. Responses prucalopride per se influence thereupon inhibition similar except that responses generally smaller. Stimulation pGC together compared alone, consistent responses. sGC stimulation hastened fade inotropic 5-HT, while altered. response activation, causing dampening downstream signalling. is able enhance increasing levels, decreases contraction independently.