Platelet adenylyl cyclase signaling remains unaltered in children undergoing hemodialysis treatment.

Patients with chronic renal failure exhibit multiple endocrine, gastrointestinal and cardiovascular abnormalities, many of which may be explained by alterations of adenylyl cyclase (AC) responsiveness and/or G-protein expression. Since such alterations were previously reported, e.g.

alpha(1)-adrenoceptor subtypes differentially couple to growth promotion and inhibition in Chinese hamster ovary cells.

We have compared the coupling of human alpha(1A)-, alpha(1B)-, and alpha(1D)-adrenoceptors (expressed at approximately 2000 fmol/mg protein in Chinese hamster ovary cells) to cellular growth promotion (as assessed by [(3)H]thymidine incorporation) and related signaling mechanisms. Maximum elevation of intracellular Ca(2+) by the three subtypes occurred with the rank order alpha(1A) (1691 nM) > alpha(1D) (1215 nM) > alpha(1B) (360 nM). In contrast, activation of the ERK, JNK, and p38 forms of mitogen-activated protein kinases occurred with the rank order alpha(1D) > alpha(1A) > alpha(1B).

Neuropeptide-Y stimulation of extracellular signal-regulated kinases in human erythroleukemia cells.

We have used human erythroleukemia (HEL) cells to investigate distal signaling mechanisms of neuropeptide-Y (NPY) receptors. NPY did not activate phospholipase D, determined as a phosphatidylethanol formation, or protein kinase C (PKC) determined enzymatically as a translocation to the plasma membrane. However, NPY caused a rapid (already maximal after 30 s) and concentration-dependent (maximum at 10-100 nM) activation of extracellular signal-regulated kinase (ERK) as assessed by immunoblotting with epitope-specific, antiphosphotyrosine antibodies and in some cases enzymatically.

Differential regulation of 46 and 54 kDa jun N-terminal kinases and p38 mitogen-activated protein kinase by human alpha(1A)-adrenoceptors expressed in Rat-1 cells.

We have investigated the alpha(1A)-adrenoceptor-mediated activation of 46 and 54 kDa isoforms of c-jun N-terminal kinase (JNK) and of p38 mitogen-activated protein kinase. The alpha(1)-adrenoceptor agonist phenylephrine activated all three kinases but with different time courses and maximal effects. Activation of all three kinases was insensitive to the phosphatidylinositol-3-kinase inhibitor wortmannin but was enhanced by the protein kinase C inhibitor bisindolylmaleimide I; a protein kinase C-activating phorbol ester inhibited JNK but not p38 activation.

Stimulation of alpha1A-adrenoceptors in Rat-1 cells inhibits extracellular signal-regulated kinase by activating p38 mitogen-activated protein kinase.

In Rat-1 fibroblasts, endothelin-1 and a protein kinase C-stimulating phorbol ester stimulated extracellular signal-regulated kinase (ERK), whereas phenylephrine, acting at stably transfected human alpha1A-adrenoceptors, inhibited basal and endothelin-1- and phorbol ester-stimulated ERK. On the other hand, phenylephrine stimulated p38 mitogen-activated protein kinase (MAPK). Anisomycin caused p38 activation and ERK inhibition quantitatively similar to those produced by phenylephrine.