The positive inotropic and XXXX -mobilizing effects of growth hormone-releasing peptides on rat heart.

@entity859 @entity2426 @entity1855 @entity23854 @entity1359 @entity460 @entity141
@entity23854 ( @entity23854 ) are synthetic peptides exerting GH-dependent or GH-independent effects via GH secretagogue receptor on many organs, including the heart. The underlying mechanisms of the cardiotropic properties of @entity23854 are poorly understood. This study investigates these effects of four @entity23854 in isolated perfused heart preparations and isolated neonatal and adult ventricular myocytes. The @entity460 response of cardiocytes to @entity23854 was visualized using confocal microscopy. All tested @entity23854 facilitated both ventricular contraction and relaxation in a dose-dependent manner, moderately decreasing coronary flow, but not modifying heart rate. @entity23854 induced a biphasic increase in intracellular free @entity141 of the cardiocytes, consisting of a transient phase (phase 1), followed by a plateau phase (phase 2). Phase 1 was abolished by pretreatment with @entity2426 , a @entity141 - @entity859 triphosphatase inhibitor of the sarcoplasmic reticulum. The phase 2 response was eliminated by removing extracellular free @entity141 , by @entity1855 , a voltage-gated @entity141 channel blocker, or by 24-h pretreatment with @entity1359 , down-regulating protein kinase C. In isolated (denervated) heart, @entity23854 have a direct cardiotropic, without chronotropic, effect. @entity23854 elevate myocardial intracellular free @entity141 through activating @entity141 influx via voltage-gated @entity141 channels and triggering @entity141 release from @entity2426 -sensitive intracellular @entity141 stores. Protein kinase C mediates the @entity23854 -induced @entity141 influx, but not @entity141 release. These finding support a number of roles for @entity23854 in the cardiovascular system.
