Abstract
Dipyrone (Dp), 4-aminoantipyrine (AA) and antipyrine (At) administered iv and Dp administered icv delay gastric emptying (GE) in rats. The participation of capsaicin (Cps)-sensitive afferent fibers in this phenomenon was evaluated. Male Wistar rats were pretreated sc with Cps (50 mg/kg) or vehicle between the first and second day of life and both groups were submitted to the eye-wiping test. GE was determined in these animals at the age of 8/9 weeks (weight: 200-300 g). Ten minutes before the study, the animals of both groups were treated iv with Dp, AA or At (240 micromol/kg), or saline; or treated icv with Dp (4 micromol/animal) or saline. GE was determined 10 min after treatment by measuring % gastric retention (GR) of saline labeled with phenol red 10 min after orogastric administration. Percent GR (mean +/- SEM, N = 8) in animals pretreated with Cps and treated with Dp, AA or At (35.8 +/- 3.2, 35.4 +/- 2.2, and 35.6 +/- 2%, respectively) did not differ from the GR of saline-treated animals pretreated with vehicle (36.8 +/- 2.8%) and was significantly lower than in animals pretreated with vehicle and treated with the drugs (52.1 +/- 2.8, 66.2 +/- 4, and 55.8 +/- 3%, respectively). The effect of icv administration of Dp (N = 6) was not modified by pretreatment with Cps (63.3 +/- 5.7%) compared to Dp-treated animals pretreated with vehicle (62.3 +/- 2.4%). The results suggest the participation of capsaicin-sensitive afferent fibers in the delayed GE induced by iv administration of Dp, AA and At, but not of icv Dp.
Highlights
The phenylpyrazolone derivatives dipyrone (Dp), 4-aminoantipyrine (AA) and antipyrine (At) administered intravenously (iv; 240 μmol/kg) delay the gastric emptying (GE) of a saline test meal in rats [1,2,3,4]
We demonstrated that the effect of Dp, AA and At administered iv on GE was completely blocked in young adult rats pretreated with Cps during the neonatal period, indicating the possibility that afferent fibers sensitive to the neurotoxin may transport the peripheral stimulus that determines the delay of emptying [6]
Percent gastric retention (GR) was significantly higher in the animals pretreated with vehicle and treated with Dp, AA, or At (52.1 ± 2.8, 66.2 ± 4, and 55.8 ± 3%, respectively) compared to saline-treated controls (32.2 ± 1.8%; Figure 1), indicating delayed GE of the test meal induced by these phenylpyrazolone derivatives
Summary
The phenylpyrazolone derivatives dipyrone (Dp), 4-aminoantipyrine (AA) and antipyrine (At) administered intravenously (iv; 240 μmol/kg) delay the gastric emptying (GE) of a saline test meal in rats [1,2,3,4]. Taken together, these studies suggest the participation of the central nervous system (CNS) and of the vagus nerve in the phenomenon. Capsaicin treatment of newborn rats has been widely used to explore the functional implications of Cps-sensitive afferent neurons. Afferent functions that are impaired by neonatal Cps comprise warmth reception and thermoregulation, cardiovascular reflexes, visceral reflexes, neuroendocrine reflexes, and satiety [5]
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