Oral administration of a centrally acting ghrelin receptor agonist to conscious rats triggers defecation

Abstract

Agonists of ghrelin receptors that cross the blood-brain barrier, but not ghrelin itself, administered peripherally (intravenous or subcutaneous), cause defecation by acting on centres in the lumbo-sacral spinal cord. It is not established whether orally administered ghrelin receptor agonists can have this action. We tested GSK894281 for its effectiveness at the ghrelin receptor and its ability to cross the blood-brain barrier. GSK894281 was effective at the human and rat ghrelin receptors at 1-10 nmol L-1, but was >1000-fold less potent at the motilin receptor. It achieved a similar blood concentration by oral or intravenous administration. Oral bioavailability was 74% and brain : blood rat..