Possible involvement of adrenomedullin in lipopolysaccharide-induced small-intestinal motility changes in conscious rats

Abstract

Our findings (1) suggest that intravenous adrenomedullin causes small-intestinal motility disturbances, and (2) support the hypothesis that adrenomedullin overproduction plays an important role in lipopolysaccharide-induced disruption of the motility pattern in the small intestine in rats.

Adrenomedullin regulates intestinal physiology and pathophysiology

“…In the small intestine of the rat, AM-like immunoreactivity is half of that detected in the stomach or in the colon [126], but among the parts of the small intestine, it seems that the ileum expresses the highest levels of preproAM mRNA [140]. Immunohistochemical visualization shows that AM-immunostained cells were localized in the mucosa, submucosa, and intestinal nerves [94].…”

“…Taken together, these data suggest that AM may be a local negative regulator of the ileal tone, acting through b 3 -adrenoreceptors, which results in PKA activation and cAMP increase. One year later, the group of Hussain et al [140] investigated the role of AM in the small-intestinal cyclic motility pattern. The small intestine exhibits a cyclic motility pattern during fasting, usually called the migrating motor complex, consisting on 3 phases: in phase 1, there is motor quiescence; phase 2 is characterized by irregular contractile activity; and finally, phase 3 is a short period of high-amplitude rhythmic contractions [167].…”

“…The small intestine exhibits a cyclic motility pattern during fasting, usually called the migrating motor complex, consisting on 3 phases: in phase 1, there is motor quiescence; phase 2 is characterized by irregular contractile activity; and finally, phase 3 is a short period of high-amplitude rhythmic contractions [167]. Intravenously administered AM dose-dependently disrupted phase 3 of the migrating motor complex [140] in rat jejunum, thus probably acting in the brain as a neurotransmitter, as far as the control of the migrating motor complex is regulated by a complex neuronal and peptidergic mechanism [167].…”

Brain or gut? Site of action of adrenomedullin to regulate gut motility

“…This evidence suggests that AM plays a role as a neurotransmitter in the brain to regulate gut functions. It is therefore speculated that AM acts in the brain to disrupt small-intestinal motility and that AM in the brain mediates the LPS-induced small-intestinal motility change observed in the study by Hussain et al 6 We do not know at this moment whether AM acts in the brain or the periphery to regulate gut motility. Further studies should be performed to clarify this problem.…”

“…1 Other peptides possibly involved in the regulation of interdigestive and postprandial intestinal motility are serotonin, 2 somatostatin, 3 pancreatic polypeptide, 4 and corticotropin-releasing hormone. 5 In this issue of the Journal of Gastroenterology, Hussain et al 6 present important data showing the role of adrenomedullin (AM) 7 in small-intestinal motility. They showed that intravenously administered AM dose-dependently disrupted phase 3 of the MMC in rats.…”