Modulation of gastric motility by brain-gut peptides using a novel non-invasive miniaturized pressure transducer method in anesthetized rodents

Abstract

Acute in vivo measurements are often the initial, most practicable approach used to investigate the effects of novel compounds or genetic manipulations on the regulation of gastric motility. Such acute methods typically involve either surgical implantation of devices or require intragastric perfusion of solutions, which can substantially alter gastric activity and may require extended periods of time to allow stabilization or recovery of the preparation. We validated a simple, noninvasive novel method to measure acutely gastric contractility, using a solid-state catheter pressure transducer inserted orally into the gastric corpus, in fasted, anesthetized rats or mice. The area under the curve of the phasic component (pAUC) of intragastric pressure (IGP) was obtained from continuous manometric recordings of basal activity and in responses to central or peripheral activation of cholinergic pathways, or to abdominal surgery. In rats, intravenous ghrelin or intracisternal injection of the thyrotropin-releasing hormone agonist, RX-77368, significantly increased pAUC while coeliotomy and caecal palpation induced a rapid onset inhibition of phasic activity lasting for the 1-h recording period. In mice, RX-77368 injected into the lateral brain ventricle induced high-amplitude contractions, and carbachol injected intraperitoneally increased pAUC significantly, while coeliotomy and caecal palpation inhibited baseline contractile activity. In wild-type mice, cold exposure (15-min) increased gastric phasic activity and tone, while there was no gastric response in corticotorpin releasing factor (CRF)-over-expressing mice, a model of chronic stress. Thus, the novel solid-state manometric approach provides a simple, reliable means for acute pharmacological studies of gastric motility effects in rodents. Using this method we established in mice that the gastric motility response to central vagal activation is impaired under chronic expression of CRF.

Gastric vagal motoneuron function is maintained following experimental spinal cord injury

“…Decades of experimental evidence has elucidated the physiological role of TRH (reviewed in Ref. ) including the vagally mediated augmentation of gastric contractions . Briefly, microinjection of TRH within the DVC excites the firing of DMV neurons, thereby stimulating efferent outflow of gastric‐projecting vagal neurons.…”

Fabrication and Implantation of Miniature Dual-element Strain Gages for Measuring <em>In Vivo</em> Gastrointestinal Contractions in Rodents.

“…The top trace represents the gastric corpus contractions from the rat during the brainstem administration of thyrotropin releasing hormone (TRH, 100 pmol), a known motility-enhancing peptide 3, 19 . It shows baseline contractions prior to the increase in phasic gastric smooth muscle activity.…”

“…This formula is less sensitive to baseline tone fluctuations that naturally occur across several seconds or minutes. Such fluctuations would have to be subtracted in order to generate valid area using under the curve measurements 3 .…”

“…For example, the utility of balloon manometry to quantify pressure changes has been questioned due to the inherent compliance of the balloon material while gastrointestinal recovery of nonabsorbable markers requires euthanizing the experimental animal for a single data point. Recently, the application and validation of a miniaturized arterial pressure catheter has been reported that offers a non-surgical method for monitoring gastric contractility in rats and mice 3 . While an orogastrically placed pressure transducer effectively eliminates confounding variables on gastrointestinal function by avoiding invasive surgical procedures, such an approach is only suitable for anesthetized preparations.…”

Adrenomedullin regulates intestinal physiology and pathophysiology

“…Several peptides can influence gut motility when injected into the brain, through modulation of autonomic nervous system activity [158]. Adrenomedullin seems to be one of these peptides because intracisternal injection of AM in conscious rats induces a dose-dependent inhibition of gastric emptying [159].…”