Primary fatty acid amide metabolism: conversion of fatty acids and an ethanolamine in N18TG2 and SCP cells

Primary fatty acid amides (PFAM) are important signaling molecules in the mammalian nervous system, binding to many drug receptors and demonstrating control over sleep, locomotion, angiogenesis, and many other processes. Oleamide is the best-studied of the primary fatty acid amides, whereas the other known PFAMs are significantly less studied. Herein, quantitative assays were used to examine the endogenous amounts of a panel of PFAMs, as well as the amounts produced after incubation of mouse neuroblastoma N(18)TG(2) and sheep choroid plexus (SCP) cells with the corresponding fatty acids or N-tridecanoylethanolamine. Although five endogenous primary amides were discovered in the N(18)TG(2) and SCP cells, a different pattern of relative amounts were found between the two cell lines. Higher amounts of primary amides were found in SCP cells, and the conversion of N-tridecanoylethanolamine to tridecanamide was observed in the two cell lines. The data reported here show that the N(18)TG(2) and SCP cells are excellent model systems for the study of PFAM metabolism. Furthermore, the data support a role for the N-acylethanolamines as precursors for the PFAMs and provide valuable new kinetic results useful in modeling the metabolic flux through the pathways for PFAM biosynthesis and degradation.     

Central Exendin‐4 Infusion Reduces Body Weight without Altering Plasma Leptin in (fa/fa) Zucker Rats

Objective: To investigate whether chronic administration of the long‐acting glucagon‐like peptide‐1 receptor agonist exendin‐4 can elicit sustained reductions in food intake and body weight and whether its actions require an intact leptin system. Research Methods and Procedures: Male lean and obese Zucker (fa/fa) rats were infused intracerebroventricularly with exendin‐4 using osmotic minipumps for 8 days. Results: Exendin‐4 reduced body weight in both lean and obese Zucker rats, maximum suppression being reached on Day 5 in obese (8%) and Day 7 in lean (16%) rats. However, epididymal white adipose tissue weight was not reduced, and only in lean rats was there a reduction in plasma leptin concentration. Food intake was maximally suppressed (by 81%) on Day 3 in obese rats but was reduced by only 18% on Day 8. Similarly, in lean rats food intake was maximally reduced (by 93%) on Day 4 of treatment and by 45% on Day 8. Brown adipose tissue temperature was reduced from Days 2 to 4. Plasma corticosterone was elevated by 76% in lean but by only 28% in obese rats. Discussion: Chronic exendin‐4 treatment reduced body weight in both obese and lean Zucker rats by reducing food intake: metabolic rate was apparently suppressed. These effects did not require an intact leptin system. Neither does the absence of an intact leptin system sensitize animals to exendin‐4. Partial tolerance to the anorectic effect of exendin‐4 in lean rats may have been due to elevated plasma corticosterone and depressed plasma leptin levels, but other counter‐regulatory mechanisms seem to play a role in obese Zucker rats.     

Sources of error in A-aDO2 calculated from blood stored in plastic and glass syringes

Wu, Eugene Y., Khalid W. Barazanji, and Robert L. Johnson,Jr. Sources of error in A-aD_O2calculated from blood stored in plastic and glass syringes.J. Appl. Physiol. 82(1):196-202, 1997.We studied the effects of time delay on bloodgases, pH, and base excess in blood stored in glass and plasticsyringes on ice and the effects of resulting errors on calculatedalveolar-to-arterial PO₂ difference(A-aD_O2).Matched samples of dog whole blood were tonometered with gasmixtures of 5% CO₂-12%O₂-83% N₂ (mixtureA), 10% CO₂-5%O₂-85%N₂ (mixtureB), and 2.88%CO₂-4% O₂-93.12%N₂ (mixtureC). Tonometered blood samples were transferred to5-ml glass (5G), 5-ml plastic (5P), and 3-ml plastic (3P) syringes andstored on ice. Blood gases were measured every 1 h up to 6 h. In 5G,PO₂ progressively decreased in bloodtonometered with mixture A but rose inblood tonometered with mixtures B and C.O₂ saturation progressively fellin all cases. In 5G, blood PCO₂progressively rose regardless of which gas mixture was used, and pH aswell as base excess progressively fell. The rise inPO₂ was faster in plastic than inglass syringes, and O₂ saturationalways rose in plastic syringes. Differences between storage in plasticand glass syringes on PO₂ change weregreatest when initial blood PO₂ washighest (mixture A). At the highestPO₂,O₂ exchange was faster in 3P thanin 5P. The rise of PCO₂ was just asfast in plastic as in glass syringes, but in both the rise inPCO₂ was faster at a higher initialPCO₂ (mixtureB) than at lower initialPCO₂ (mixturesB and C). Rates ofPO₂ andPCO₂ change in matched samples weresignificantly faster in 3P than in 5P. Errors due to rises inPCO₂ andPO₂ cause additive errors incalculatedA-aD_O2,and when blood is stored in plastic syringes for >1 h significant errors result. Errors are greater in normoxic blood, in which estimatedA-aD_O2decreased by >10 Torr after 6 h on ice in plastic syringes, than inhypoxic blood.

     

Renal, cardiovascular and endocrine effects of centrally administered galanin in the anaesthetised rat.

Several studies implicate galanin as a central neuromodulator with an ability to influence hypothalamic and pituitary secretion. Central galanin content is also sensitive to the state of body hydration. Cardiovascular, renal and peripheral endocrine changes evoked by intracerebroventricular administration of galanin have been examined in the anaesthetized rat. Central galanin infusion consistently induced a transitory diuresis, the increase in urine flow being associated with a reduction in urine osmolality. There was no demonstrable change in plasma vasopressin concentration at the end of a 40 min galanin infusion. However, plasma aldosterone and corticosterone concentrations were significantly reduced by comparison with time-matched vehicle infused controls. There were no clear changes in renal electrolyte excretion or in heart rate or mean arterial blood pressure during the study period. The findings of this study support a participatory role for galanin in body fluid homeostasis, though the mechanisms responsible for mediating its central action on urine production remain unclear.