PPARα stimulates the rat gastrin-producing cell

The peroxisome proliferator (PP) ciprofibrate stimulates gastrin-producing cells (G-cells) in the rat stomach by an unknown mechanism, inducing hypergastrinemia and secondary enterochromaffin-like (ECL) cell hyperplasia. Ciprofibrate is a specific ligand for the nuclear peroxisome proliferator-activated receptor α (PPARα). To see whether the effects of ciprofibrate could be imitated, rats were given another PPARα ligand WY-14643 or the PPARγ ligand troglitazone by gastric intubations daily for 28 and 56 days. Troglitazone failed to raise gastrin levels. WY-14643 increased gastrin mRNA abundance, G-cell density and induced hypergastrinemia, but to a lesser extent than ciprofibrate. ECL cell parameters increased in proportion with the relative hypergastrinemia. Ciprofibrate and WY-14643 altered the levels of acyl CoA-oxidase mRNA and PPARα mRNA in antrum, but had no effect in corpus. The PPARα receptor was found in at least some G-cells by immunostaining. This study supports the hypothesis that PPARα specific ligands could stimulate the G-cells by acting locally from the stomach lumen through antral PPARα. [Copyright &y& Elsevier]