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.

Endothelin has steroidogenic activity in adrenal glomerulosa cells, as do two other vasoconstrictor peptides, angiotensin II and vasopressin. The steroidogenic activities of angiotensin II and vasopressin are probably mediated via the phosphatidylinositol-turnover pathway and associated changes in cytosolic Ca2+ concentration. Endothelin caused a steroidogenic response, which was small compared with that to angiotensin II and quantitatively similar to the vasopressin response. Cytosolic free Ca2+ responses were similarly higher to angiotensin II than to either of the other two peptides. However, total inositol phosphate responses to endothelin and angiotensin II were similar when these were measured over 20 min, and were quantitatively greater than the vasopressin response. A detailed study has been made of the phosphatidylinositol-turnover response to endothelin in comparison with responses to angiotensin II and vasopressin. Each of the three peptides produced a rapid and transient rise in Ins(1,4,5)P3 (max. 5-15 s), followed by a slow sustained rise. Ins(1,4,5)P3 was metabolized by both dephosphorylation and phosphorylation pathways, but the relative importance of the two metabolic pathways was different under stimulation by each of the three peptides. These findings show that adrenal glomerulosa cells can distinguish between the stimulation of phosphatidylinositol turnover by three different effectors. These differences in the pathway may be associated with the observed different steroidogenic and Ca2+ responses to the three peptides.

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1. Endothelin (ET), vasopressin (VP) and angiotensin II (AII) all stimulate aldosterone production in adrenal glomerulosa cells but the response to AII is greater than that to either ET or VP. 2. Total inositol phosphate responses to AII and ET were similar but the response to VP was lower. 3. Cytosolic free Ca2+ responses to AII were higher than to either of the other peptides. 4. Metabolism of 145IP3 was different under stimulation by the three different peptides. 5. Adrenal glomerulosa cells can distinguish between three different agonists which stimulate phosphatidylinositol turnover and produce a selective response to each peptide.