Abstract
Antipyrine (At) and dipyrone (Dp) delay gastric emptying (GE) in rats. The objective of the present study was to assess the effects of intravenous (iv) and intracerebroventricular (icv) administration of At and Dp on the GE of liquid by rats. GE was assessed in male Wistar rats (5-10 in each group) 10 min after the icv or iv drug injection by measuring percent gastric retention (%GR) of a saline test meal labeled with phenol red 10 min after administration by gavage. The At iv group was significantly higher (64.4 +/- 2.6%) compared to control (33.4 +/- 1.5%) but did not differ from the Dp group (54.3 +/- 3.8%). After icv administration of At, %GR (34.2 +/- 2%) did not differ from control (32.6 +/- 1.9%), but was significantly higher after Dp (54.5 +/- 2.3%). Subdiaphragmatic vagotomy significantly reduced %GR in the At group (30.2 +/- 0.7%) compared to the sham group, but was significantly higher than in the controls (23.0 +/- 0.5%). In the animals treated with At iv, baclofen significantly reduced %GR (28.3 +/- 2.4%) compared to vehicle-treated animals (55.2 +/- 3.2%). The same occurred in the animals treated iv with vehicle and icv with baclofen. Although vagotomy and baclofen reduced %GR per se, the reduction was twice more marked in the animals treated with At. The results suggest that At administered iv, but not icv, delays GE of liquid in rats with the participation, at least in part, of the vagus nerve and that this phenomenon is blocked by the activation of GABA B receptors in the central nervous system.
Highlights
Gastric emptying (GE) is the process of the transfer of the gastric content to the small intestine as the result of the motor activity of the stomach, pylorus and duodenum under control of inhibitory and stimulatory mechanisms [1].Non-steroidal anti-inflammatory drugs are among the most frequently prescribed drugs in the world and have been extensively studied because of their gastrointestinal toxicity
The results suggest that At administered iv, but not icv, delays gastric emptying (GE) of liquid in rats with the participation, at least in part, of the vagus nerve and that this phenomenon is blocked by the activation of GABAB receptors in the central nervous system
Vagotomy significantly reduced %GR in the animals treated with At compared to the sham group (VgXAt vs shamAt) and the same phenomenon was observed among the animals that received vehicle (VgXC vs shamC); the reduction was twice higher in the animals that received At (a 47.8% reduction in mean %GR) compared to control (a 23.8% reduction in mean %GR)
Summary
Gastric emptying (GE) is the process of the transfer of the gastric content to the small intestine as the result of the motor activity of the stomach, pylorus and duodenum under control of inhibitory and stimulatory mechanisms [1].Non-steroidal anti-inflammatory drugs are among the most frequently prescribed drugs in the world and have been extensively studied because of their gastrointestinal toxicity. Dipyrone (Dp), a phenylpyrazolone derivative mainly used for its antipyretic and analgesic properties, causes delayed GE in rats when administered at high doses [7]. This effect was confirmed using a dose of 80 mg/kg (240 μmol/kg) administered intravenously (iv) and saline solution as a test meal [8]. A recent study in which Dp was administered iv and intracerebroventricularly (icv) to rats has suggested that this effect may be due to the action of the drug on the central nervous system (CNS), with the participation of the paraventricular nucleus and of the vagus nerve [9]. Additional observations have demonstrated that this phenomenon is blocked by icv administration of baclofen (bac), a GABAB receptor agonist [10]
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