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Biomedical subjects

G Arslan

Publications and source records attributed to G Arslan.

At least 73 records · Page 4Linked to original sources

Differences in the order of potency for agonists but not antagonists at human and rat adenosine A2A receptors.

To examine possible species differences in pharmacology, rat adenosine A2A receptors were studied in PC12 (pheochromocytoma) cells, and human receptors in Chinese hamster ovary (CHO) cells transfected with the cloned human A2A receptor cDNA. Using [3H]-5-amino-7(2-phenylethyl)-2-(2-furyl)-pyrazolo[4,3-e]-1,2,4-triazolo [1,5-c]pyrimidine ([3H]-SCH 58261) as radioligand, the estimated Bmax (maximal binding) was 538 and 2085 fmol/mg in CHO and PC12 cells, respectively. The Kd (dissociation constant) values for [3H]-SCH 58261 were 1.05 and 5.6 nM in the two cell types, respectively. The order of potency of antagonists and most agonists was the same in both cell types, but 2-phenylaminoadenosine and 2-chloroadenosine were relatively less potent in PC12 cells than in CHO cells. In the functional assay, using cyclic AMP accumulation, all agonists tested were more potent in CHO than in PC12 cells, but this could not be readily explained by differences in adenylyl cyclase or in the expression of G proteins. As in the case of binding, the relative agonist potencies were similar for most compounds, but 2-phenylaminoadenosine and 2-chloroadenosine were more potent at human A2A receptors in CHO cells than predicted from the data obtained on rat A2A receptors in PC12 cells. Antagonists were approximately equipotent in the two cells. These results show that, despite only small differences in amino acid sequences and no difference in antagonist pharmacology, the relative order of potency of receptor agonists can differ between species homologues of the adenosine A2A receptor.

Adenosine↗

Signaling via A2A adenosine receptor in four PC12 cell clones.

PC12 cells are genetically labile and so-called wild-type cells comprise multiple subclones. We have examined the A2A adenosine receptor signal transduction pathways in four such clones (denoted clones 1, 19, 21 and 27) of PC12 cells. Adenosine A2A, A2B and A1 receptor mRNAs were detected in all four clones by RT-PCR, whereas no A3 receptor mRNA was found. A2A receptors were quantitated by radioligand binding using the antagonist radioligand [3H]SCH 58261 ([3H]-5-amino-7(2-phenylethyl)-2-(2-furyl)-pyrazolo[4,3-e]-1,2,4 triazolo [1,5-c] pyrimidine). The Bmax was highest in clone 1 followed by clones 21, 19 and 27. Whereas the amount of G(i) protein appeared similar in all four clones, the amount of G(s) protein was higher in clones 21 and 27 than in the other two clones. Maximal responses to the non-selective adenosine analogue NECA (5'-N-ethylcarboxamidoadenosine) were similar to those observed with the selective adenosine A2A receptor agonist CGS 21680 (2-[p-(2-carbonylethyl) phenylethylamino]-5'-N-ethylcarboxamidoadenosine), and were approximately equal in clones I and 21, but lower in clone 19 and very low in clone 27. For both compounds EC50 was significantly higher in clone 27 than in clone 1. In both clones the response to NECA could be competitively antagonized by a selective adenosine A2A antagonist, SCH 58261. The present results show that different clones of PC 12 cells differ widely in the cAMP increase induced by adenosine analogues and that this is due to differences in the amount of adenosine A2A receptor, G protein and effector. A large difference in receptor number resulted in differences in potency of an agonist.

Adenosine↗

Is pancreatitis a complication of propofol infusion?

The effects of bolus and infusion doses of propofol on histopathological changes in the rat pancreas are reported. After obtaining Hospital Ethics Committee approval, 75 female Wistar rats were assigned to three study groups. Groups I (n = 30) and II (n = 30) received 10 mg kg-1 intravenous bolus of propofol; with propofol administered to group II at an infusion rate of 10 mg kg-1 h-1 for 30 min immediately after the bolus doses. Group III (n = 15) was used as the control group. Twenty-four hours after propofol administration blood samples and pancreatic tissue specimens were obtained under ether anaesthesia. Plasma cholesterol, triglyceride, amylase, and lipase levels were studied, and pancreatic tissues were examined under light microscopy. Plasma cholesterol and triglyceride levels were significantly higher in group II compared with the other groups. Differences between the groups in respect of plasma amylase and lipase levels were not statistically significant. Acute pancreatitis was observed under light microscopy, in three rats (10%) in group II, and in one rat (6.6%) in the control group. The pancreatic tissues of group I were normal. The incidence of acute pancreatitis in each of the groups was not significant. It is therefore suggested that, further controlled studies are needed to investigate the relation between pancreatitis and the use of propofol.

Acute Disease↗

Renal colic: comparison of spiral CT, US and IVU in the detection of ureteral calculi.

The aim of our study was to compare non-contrast spiral CT, US and intravenous urography (IVU) in the evaluation of patients with renal colic for the diagnosis of ureteral calculi. During a period of 17 months, 112 patients with renal colic were examined with spiral CT, US and IVU. Fifteen patients were lost to follow-up and excluded. The remaining 97 patients were defined to be either true positive or negative for ureterolithiasis based on the follow-up data. Sensitivity, specificity, positive and negative predictive value and accuracy of spiral CT, US and IVU were determined, and secondary signs of ureteral stones and other pathologies causing renal colic detected with these modalities were noted. Of 97 patients, 64 were confirmed to have ureteral calculi based on stone recovery or urological interventions. Thirty-three patients were proved not to have ureteral calculi based on failure to recover a stone and diagnoses unrelated to ureterolithiasis. Spiral CT was found to be the best modality for depicting ureteral stones with a sensitivity of 94 % and a specificity of 97 %. For US and IVU, these figures were 19, 97, 52, and 94 %, respectively. Spiral CT is superior to US and IVU in the demonstration of ureteral calculi in patients with renal colic, but because of its high cost, higher radiation dose and high workload, it should be reserved for cases where US and IVU do not show the cause of symptoms.

Adult↗