Different pathways of inositol phosphate metabolism in intact neonatal rat hearts and isolated cardiomyocytes

Abstract

In most tissues stimulation of the phosphatidylinositol turnover pathway causes release of inositol 1,4,5-trisphosphate [Ins(1,4,5)P3], which is subsequently metabolized to a wide range of inositol phosphate isomers deriving from both phosphorylation and dephosphorylation reactions. However, addition of noradrenaline to isolated intact neonatal-rat hearts generated only those inositol phosphates produced by dephosphorylation of Ins(1,4,5)P3. Products of the InsP3 kinase pathway were absent from the profiles, except after prolonged stimulation. In contrast, addition of noradrenaline to isolated cultured neonatal-rat cardiomyocytes caused the release of Ins(1,4,5)P3, which was metabolized by both phosphorylation and dephosphorylation pathways to yield a complex range of inositol phosphate isomers, as observed in many other cell types. These differences between the responses in intact tissues and in isolated cell preparations were not caused by the different conditions used for [3H]inositol labelling. Furthermore, results could not be explained by overgrowth of other cell types in the isolated cell preparations. Thus the results demonstrate that the isolation and culture of rat neonatal cardiomyocytes produces alterations in the nature of the phosphatidylinositol turnover pathway.

Effect of Concomitant β‐Adrenoceptor Stimulation on α1‐Adrenoceptor‐Mediated Increase of Inositol‐1, 4, 5‐trisphosphate Mass in Adult Rat Cardiomyocytes

“…Also, inositol phosphates may be formed from other sources than IP3, in particular in intact cardiac tissue . It is worth noting that Guse et al (1991) found a 6-8-fold increase in the level of radiolabelled IP3 after al-adrenoceptor stimulation, which is well above the 2-3-fold increase most investigators have observed when using incorporation of radiolabelled inositol (Steinberg et al 1989;Ventura et al 1991;Woodcock et al 1992Woodcock et al & 1993. Furthermore, the transient nature of the inhibitory effect reported by Guse et al (1991) is not easily reconciled with the mechanisms currently believed to be involved in the modulation of the phosphoinositide system by CAMP-elevating compounds in various cell types, e.g.…”

“…Also, both the time course and the magnitude of the IP, accumulation in response to purinergic stimulation of adult rat cardiomyocytes (Puceat & Vassort 1996) were very similar to the response observed after a,-adrenoceptor stimulation in the present study. In most studies that examined the accumulation of radiolabelled ( i,4,5)IP3, an initial, 2-3-fold increase was observed (Steinberg et al 1989;Ventura et al 1991;Woodcock et al 1992Woodcock et al & 1993, although Guse et al (1989) found an increase that was at least 8-fold. The increased IP, levels either declined to control values within 1-2 min.…”

“…(Steinberg et al 1989;Ventura et al 1991), or remained elevated above control levels for up to 15-20 min. (Guse et al 1989;Woodcock et al 1992Woodcock et al & 1993. Some of these differences may reflect differences in the labelling protocol, as well as different characteristics of cardiomyocytes isolated from neonatal or adult rats.…”

Inositol phospholipids localized to caveolae in rat heart are regulated by α1-adrenergic receptors and by ischemia-reperfusion

“…␣ 1 -AR are not detected on mast cells or cardiac fibroblasts and thus contribution to norepinephrine-dependent responses from these cell types can be discounted. Furthermore, PLC responses in cardiomyocytes differ in terms of rate and in inositol phosphate isomers generated from responses in other cell types (51).…”

STIMULATION OF PHOSPHATIDYLINOSITOL TURNOVER IN ADULT RAT LEFT ATRIA DOES NOT INVOLVE RELEASE OF INOSITOL (1,4,5) TRI SPHOSPHATE

“…The most likely explanation of the data is that receptor stimulation leads primarily to the release of Ins(l,4)P2 which is broken down to Ins(4)Pl and a little Ins(1)PI. Only a small amount of Ins(1,4,5)P3 is released and this accounts for the absence of phosphorylation products of the compound (Woodcock et al 1987).…”