Central corticotropin-releasing factor (CRF) plays an important role in mediating restraint stress-induced delayed gastric emptying. However, it is unclear how restraint stress modulates gastric motility to delay gastric emptying. Inasmuch as solid gastric emptying is regulated via antropyloric coordination, we hypothesized that restraint stress impairs antropyloric coordination, resulting in delayed solid gastric emptying in conscious rats. Two strain gauge transducers were sutured onto the serosal surface of the antrum and pylorus, and postprandial gastric motility was monitored before, during, and after restraint stress. Antropyloric coordination, defined as a propagated single contraction from the antrum to the pylorus within 10 s, was followed by ≥20 s of quiescence. Restraint stress enhanced postprandial gastric motility in the antrum and pylorus to 140 ± 9% and 134 ± 9% of basal, respectively ( n = 6). The number of episodes of antropyloric coordination before restraint stress, 2.4 ± 0.4/10 min, was significantly reduced to 0.6 ± 0.3/10 min by restraint stress. Intracisternal injection of the CRF type 2 receptor antagonist astressin 2B (60 μg) or guanethidine partially restored restraint stress-induced impairment of antropyloric coordination (1.6 ± 0.3/10 min, n = 6). The restraint stress-induced augmentation of antral and pyloric contractions was increased by astressin 2B and guanethidine but abolished by atropine, hexamethonium, and vagotomy. Restraint stress enhanced postprandial gastric motility via a vagal cholinergic pathway. Restraint stress-induced delay of solid gastric emptying is due to impairment of antropyloric coordination. Restraint stress-induced impairment of antropyloric coordination might be mediated via a central CRF pathway.
Physiologically‐Based Pharmacokinetic Modeling of Atorvastatin Incorporating Delayed Gastric Emptying and Acid‐to‐Lactone Conversion
