Biomedical subjects

Agnes Kittel

Publications and source records attributed to Agnes Kittel.

6 recordsLinked to original sources

PubMed2005

Endotoxin can decrease isolated rat parotid acinar cell amylase secretion in a nitric oxide-independent manner.

Salivary mucus and amylase have an anti-bacterial nature. Bacterial endotoxin is considered to decrease mucus secreting cell activity by nitric oxide-dependent mechanisms. In this study, the actions of endotoxin on amylase secreting cell activity have been studied. Endotoxin (Escherichia coli lipopolysaccharide; 3 mg/kg, i.v., 5 h) evoked nitric oxide synthase 2 (NOS2) induction in the rat whole parotid tissue (assessed by Western blot and the citrulline assay) and in rat isolated parotid acinar cells (assessed by Western blot and immunohistochemistry), and reduced basal and acetylcholine-stimulated amylase secretion from these isolated cells. However, N(G)-nitro-L-arginine methyl ester (0.1 mg/ml, 4 days in drinking water, yielding a dose of 25 mg/kg/day) did not affect amylase release under basal or acetylcholine-stimulated conditions, either in control acinar cells or those from endotoxin challenged rats. Thus, basal, acetylcholine-evoked or endotoxin-decreased cellular amylase secretion from rat isolated parotid acinar cells does not appear to be modulated by endogenous nitric oxide.

Acetylcholine↗

PubMed2005

Expression of NTPDase1 and caveolins in human cardiovascular disease.

Pathological circumstances like inflammation or ischemic insult facilitate the release of adenine nucleotides from several types of cells. These extracellular nucleotides are rapidly converted to adenosine by ectonucleotidases, mainly ectonucleoside triphosphate diphosphohydrolase1 (NTPDase1/CD39) and CD73. NTPDase1/CD39 can interact with caveolins, structural proteins of signal-transducing microdomains termed caveolae. Caveolins are thought to have physiological roles in heart ageing and cardiac diseases. The aim of this study was to investigate the expression of NTPDase1 together with caveolins in chronic human cardiovascular diseases and elucidate their role in human heart. The HPLC analysis showed significant increase in ATPase activity in pathological samples from patients with ischemic heart disease. Immunostaining also showed alterations in the expression and distribution of NTPDase1. Caveolin-1 and caveolin-2 expression was much alike in control and pathological cases, while expression of caveolin-3 was lower in pathological samples. Changes in the expression of NTPDase1 and caveolins seem to be independent of human cardiovascular disease.

Adenosine Triphosphatases↗

PubMed2005

Increased sensitivity of striatal dopamine release to H2O2 upon chronic rotenone treatment.

It is believed that both mitochondrial dysfunction and oxidative stress play important roles in the pathogenesis of Parkinson's disease (PD). We studied the effect of chronic systemic exposure to the mitochondrial inhibitor rotenone on the uptake, content, and release of striatal neurotransmitters upon neuronal activity and oxidative stress, the latter simulated by H(2)O(2) perfusion. The dopamine content in the rat striatum is decreased simultaneously with the progressive loss of tyrosine hydroxylase (TH) immunoreactivity in response to chronic intravenous rotenone infusion. However, surviving dopaminergic neurons take up and release only a slightly lower amount of dopamine (DA) in response to electrical stimulation. Striatal dopaminergic neurons showed increased susceptibility to oxidative stress by H(2)O(2), responding with enhanced release of DA and with formation of an unidentified metabolite, which is most likely the toxic dopamine quinone (DAQ). In contrast, the uptake of [(3)H]choline and the electrically induced release of acetylcholine increased, in coincidence with a decline in its D(2) receptor-mediated dopaminergic control. Thus, oxidative stress-induced dysregulation of DA release/uptake based on a mitochondrial deficit might underlie the selective vulnerability of dopaminergic transmission in PD, causing a self-amplifying production of reactive oxygen species, and thereby contributing to the progressive degeneration of dopaminergic neurons.

Acetylcholine↗

PubMed2004

ATP and ATPase secretion by exocrine pancreas in rat, guinea pig, and human.

ATP is an extracellular regulator in numerous physiological and pathologic processes. Recently, 7 different subtypes of purinoceptors were identified on either the basolateral or the luminal membrane of pancreatic duct cells. However, the in vivo regulatory role of ATP in pancreatic function has not been established. We investigated the possible regulatory role of endogenous ATP in pancreatic function by measuring ATP concentrations and ATPase activity in pancreatic juice obtained from anesthetized rats and guinea pigs and from human patients undergoing endoscopy. Juice was collected from the main pancreatic duct in rats and guinea pigs under basal conditions or during stimulation with CCK, bombesin, or secretin. In guinea pigs, CCK, bombesin, and secretin did not affect ATP output, although they did stimulate fluid secretion. ATPase activity in the juice was evaluated by measuring the rate of hydrolysis of added ATP. Consistent with the low ATP concentrations in rat pancreatic juice, we found high levels of ATPase activity in this species. This was confirmed by HPLC, which also showed the metabolites of ATP hydrolysis. Ecto-ATPase activity was demonstrated by enzyme histochemistry in both the pancreatic acini and ducts in rats, but it was not detectable in guinea pigs and humans. These differences in ATP levels and ATPase expression may indicate significant species differences in the purinergic regulation of pancreatic secretion.

Adenosine Triphosphatases↗

PubMed2004

Localization of nucleoside triphosphate diphosphohydrolase-1 (NTPDase1) and NTPDase2 in pancreas and salivary gland.

Ectonucleoside triphosphate diphosphohydrolases (NTPDases) are membrane-bound ectoenzymes that hydrolyze extracellular nucleotides. We investigated the distribution of NTPDase1 and NTPDase2 in murine salivary gland and pancreas. Histochemistry and immunostaining (by both light and electron microscopy), combined with functional assays, were used to describe the localization patterns and enzyme activities in the organs of wild-type and NTPDase1/cd39-null mice. Pancreatic acinar cells and salivary gland acinar/myoepithelial cells were positive for NTPDase1 and NTPDase2. Ecto-ATPase activity was slightly higher in salivary glands. Ductal epithelial cells expressed ecto-ATPase activity but NTPDase1 and NTPDase2 expression were weak at best. ATPase activity was found in blood vessels of both tissues and its localization pattern overlapped with NTPDase1 staining. In these structures, NTPDase2 antibodies stained the basolateral aspect of endothelial cells and the supporting cells. Biochemical assays and histochemical staining showed relatively high levels of ATPase activity in both glands of cd39(-/-) mice. Our data therefore support a physiological role for NTPDase2 and other ectonucleotidases in the pancreas and salivary glands. Because NTPDase1 is expressed in non-vascular cell types, this finding suggests that NTPDase1 may have functions in the gastrointestinal tract that differ from those demonstrated in the vascular system.

Adenosine Triphosphatases↗

PubMed2002

Localization of NTPDase1/CD39 in normal and transformed human pancreas.

Elevated levels of extracellular ATP have been observed in many tumors. We have localized NTPDase1/CD39, one of the principal extracellular nucleotide-hydrolyzing enzymes, in normal and cancerous human pancreas. NTPDase/E-ATPDase activity was demonstrated with an enzyme histochemical technique on cryosections of human pancreas. Acinar and duct epithelial cells were devoid of E-ATPDase activity in both normal and transformed tissue. Endothelial cells and smooth muscle around blood vessels and larger ducts showed strong activity. Nerves, connective tissue, and the beta-cells of the islets were also stained. In cancerous tissue this activity was diminished in the smooth muscle around the ducts and was absent from newly formed connective tissue. Immunostaining for CD39 supported these results but revealed the presence of inactive CD39 in the duct epithelial cells. We hypothesize that the significantly diminished activity of NTPDase1 in the tissues surrounding the ducts may be associated with the processes that lead to tumor formation in human pancreas.

Adenosine Triphosphatases↗