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Pancreatic polypeptide (PP) is an anorexigenic hormone released from pancreatic F cells upon food intake. We aimed to determine the effect of PP on gastric accommodation and gastric emptying in conscious Wistar HAN rats to investigate whether effects on motor function could contribute to its anorexigenic effects. Intragastric pressure (IGP) was measured through a chronically implanted gastric fistula during the infusion of a nutrient meal (Nutridrink; 0.5 ml/min). Rats were treated with PP (0, 33 and 100 pmol.kg-1.min-1) in combination with NG-nitro-L-arginine methyl ester (L-NAME; 180 mg.kg-1.h-1), atropine (3 mg.kg-1.h-1), or vehicle. Furthermore, the effect of PP was tested after subdiaphragmal vagotomy of the stomach. Gastric emptying of a noncaloric and a caloric meal after treatment with 100 pmol.kg-1.min-1 PP or vehicle was compared using X-rays. PP significantly increased IGP during nutrient infusion compared with vehicle (P < 0.01). L-NAME and atropine significantly increased IGP during nutrient infusion compared with vehicle treatment (P < 0.005 and 0.01, respectively). The effect of PP on IGP during nutrient infusion was abolished in the presence of L-NAME and in the presence of atropine. In vagotomized rats, PP increased IGP compared with intact controls (P < 0.05). PP significantly delayed gastric emptying of both a noncaloric (P < 0.05) and a caloric (P < 0.005) meal. PP inhibits gastric accommodation and delays gastric emptying, probably through inhibition of nitric oxide release. These results indicate that, besides the well-known centrally mediated effects, PP might decrease food intake through peripheral mechanisms. [ABSTRACT FROM AUTHOR]

Background/Aims: Our aim was to investigate whether muscarinic and nicotinic receptors mediate nitric oxide release during motor events in the rat stomach. Methods: Isolated rat stomach volume changes were monitored in an organ bath setup with an intragastric balloon coupled to a barostat and studied in basal conditions and during electrical vagal stimulation (EVS). In conscious rats, the intragastric pressure (IGP) was measured during test meal infusion. Results: In the presence of NG-nitro-L-arginine methyl ester (L-NAME; 0.1 mmol/l), EVS induced significant gastric contractions (mean ± SEM = 0.27 ± 0.04 ml; n = 6) that could be blocked by atropine (3 μmol/l) and hexamethonium (0.1 mmol/l). In the presence of atropine and/or hexamethonium, EVS-induced relaxations could not be blocked by L-NAME, while exogenous nitric oxide could still relax the stomach. In conscious rats, atropine (1 mg kg–1) initially decreased IGP, while during further distension it increased IGP. In the presence of L-NAME (30 mg kg–1) atropine consistently decreased IGP. L-NAME alone significantly increased IGP during the test meal infusion, but this effect was reduced in the presence of atropine. Conclusion: These findings indicate a role for nicotinic and muscarinic receptors in the vagal-stimulation-induced activation of nitrergic nerves in the rat stomach. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background Cerebral evoked potentials (CEP) induced by colorectal distension (CRD) in conscious rats provides a novel method in studies of visceral sensitivity. The aim of this study was to explore the pharmacological effect on CEP of compounds known to reduce the visceromotor response to CRD. Methods Epidural electrodes were chronically implanted in eight female Sprague-Dawley rats. Evoked potentials were elicited by colorectal rapid balloon distensions (100 ms, 80 mmHg) and the effect of WIN55 (cannabinoid CB receptor agonist), clonidine (adrenergic α 2 receptor agonist), MPEP (mGluR5 receptor antagonist), pregabalin (ligand of α 2 δ subunits in voltage-gated calcium channels) and baclofen (GABA-B receptor agonist) on amplitudes and latency of CEP were determined. Results WIN55 (0.1 μmol kg −1 ), clonidine (0.05 μmol kg −1 ), MPEP (10 μmol kg −1 ) and pregabalin (200 μmol kg −1 ) caused a significant, p < 0.05, reduction of the N2 to P2 peak-to-peak amplitude by 23 ± 8%, 25 ± 8%, 39 ± 5%, and 47 ± 6% respectively. Baclofen (9 μmol kg −1 ) induced a prolongation of the N2 peak latency of 18 ± 4% but had no significant effect on the amplitudes. Conclusion The obtained results suggest that MPEP, WIN55, clonidine, and pregabalin reduce visceral nociceptive input to the brain, whereas the lack of effect of baclofen on CRD evoked CEP amplitudes suggest that the effect on VMR is not due to a direct analgesic effect. Brain responses to colorectal distension provide a useful tool to evaluate pharmacological effects in rats and may serve as a valuable preclinical model for understanding pharmacological mechanisms related to visceral sensitivity. [ABSTRACT FROM AUTHOR]