1.Complex interactions of NO/cGMP/PKG systems on Ca2+ signaling in afferent arteriolar vascular smooth muscle.
Fellner SK1, Arendshorst WJ. Am J Physiol Heart Circ Physiol. 2010 Jan;298(1):H144-51. doi: 10.1152/ajpheart.00485.2009. Epub 2009 Oct 30.
Little is known about the effects of nitric oxide (NO) and the cyclic GMP (cGMP)/protein kinase G (PKG) system on Ca(2+) signaling in vascular smooth muscle cells (VSMC) of resistance vessels in general and afferent arterioles in particular. We tested the hypotheses that cGMP-, Ca(2+)-dependent big potassium channels (BK(Ca(2+))) buffer the Ca(2+) response to depolarization by high extracellular KCl and that NO inhibits adenosine diphosphoribose (ADPR) cyclase, thereby reducing the Ca(2+)-induced Ca(2+) release. We isolated rat afferent arterioles, utilizing the magnetized microsphere method, and measured cytosolic Ca(2+) concentration ([Ca(2+)](i)) with fura-2, a preparation in which endothelial cells do not participate in [Ca(2+)](i) responses. KCl (50 mM)-induced depolarization causes an immediate increase in [Ca(2+)](i) of 151 nM. The blockers N(omega)-nitro-L-arginine methyl ester (of nitric oxide synthase), 1,2,4-oxodiazolo-[4,3-a]quinoxalin-1-one (ODQ, of guanylyl cyclase), KT-5823 (of PKG activation), and iberiotoxin (IBX, of BK(Ca(2+)) activity) do not alter the [Ca(2+)](i) response to KCl, suggesting no discernible endogenous NO production under basal conditions.
2.Implication of protein kinase A for a hepato-protective mechanism of milrinone pretreatment.
Satoh K1, Kume M, Abe Y, Uchinami H, Yakubouski SV, Takahashi T, Sato T, Yamamoto Y. J Surg Res. 2009 Jul;155(1):32-9. doi: 10.1016/j.jss.2008.07.004. Epub 2008 Aug 15.
BACKGROUND: We have previously reported that an increase of adenosine 3',5'-cyclic monophosphate (cAMP) in liver tissue after an administration of milrinone, a phosphodiesterase-3 inhibitor attenuates hepatic warm ischemia-reperfusion injury. The aim of this study was to determine whether cAMP-dependent protein kinase (protein kinase A) activation was involved in the milrinone-induced hepatoprotective effect on an ischemia-reperfusion injury in an in vivo model.
3.Regulation of protein kinases and coregulatory interplay of S-100beta and serotonin transporter on serotonin levels in diabetic rat brain.
Ramakrishnan R1, Sheeladevi R, Namasivayam A. J Neurosci Res. 2009 Jan;87(1):246-59. doi: 10.1002/jnr.21833.
Protein kinases are critical component in the regulation of signal transduction pathways, including neurotransmitters. Our previous studies have shown that serotonin (5-HT) altered under diabetic condition was accompanied by alterations of protein kinase C-alpha (PKC-alpha) and CaMKII, and those alterations were reversed after insulin administration. The current study showed that alloxan-induced diabetic animals revealed hyperglycemia and was associated with an increase in the content of 5-HT, PKC-alpha expression and PKC activity (P < 0.05) simultaneously in striatum (ST), midbrain (MB), pons medulla (PM), cerebellum (CB), and cerebral cortex (CCX) from 7 days to 60 days. Although the 5-HT levels in hippocampus (HC) and hypothalamus (HT) were not altered, the PKC-alpha expression and PKC activity showed increases (P < 0.05) in level in HC. Insulin administration reversed all these changes to a normal level. In contrast, the in vitro study has shown that the 5-HT levels correlated with PKC-alpha expressions as well as PKC activity (P < 0.
4.Cell-specific effects of luminal acid, bicarbonate, cAMP, and carbachol on transporter trafficking in the intestine.
Jakab RL1, Collaco AM, Ameen NA. Am J Physiol Gastrointest Liver Physiol. 2012 Oct 15;303(8):G937-50. doi: 10.1152/ajpgi.00452.2011. Epub 2012 Aug 30.
Changes in intestinal luminal pH affect mucosal ion transport. The aim of this study was to compare how luminal pH and specific second messengers modulate the membrane traffic of four major ion transporters (CFTR, NHE3, NKCC1, and NBCe1) in rat small intestine. Ligated duodenal, jejunal, and ileal segments were infused with acidic or alkaline saline, 8-Br-cAMP, or the calcium agonist carbachol in vivo for 20 min. Compared with untreated intestine, lumen pH was reduced after cAMP or carbachol and increased following HCO(3)(-)-saline. Following HCl-saline, lumen pH was restored to control pH levels. All four secretory stimuli resulted in brush-border membrane (BBM) recruitment of CFTR in crypts and villi. In villus enterocytes, CFTR recruitment was coincident with internalization of BBM NHE3 and basolateral membrane recruitment of the bicarbonate transporter NBCe1. Both cAMP and carbachol recruited NKCC1 to the basolateral membrane of enterocytes, while luminal acid or HCO(3)(-) retained NKCC1 in intracellular vesicles.