Context: Ghrelin is a novel hormone produced mainly in the gastric body. Hitherto, mapping studies of ghrelin cells covering the entire GI-tract in humans have been lacking. Further, the phenotype of extragastric ghrelin cells is not known.

Objective: To perform a detailed mapping with specimens from all parts of the GI-tract, and co-localisation studies to phenotype ghrelin cells along the tract. In addition, mapping of ghrelin cells was performed in porcine GI-tract, and the plasma profiles of ghrelin and motilin in blood from the porcine intestine were measured.

Design: Biopsies from patients were obtained during gastroscopy or surgery. Ghrelin cell density and phenotyping was assessed with immunocytochemistry, in situ hybridisation, and immunogold electron microscopy. Plasma ghrelin and motilin levels were measured in pigs, fitted with cannulas in the mesenteric vein.

Results: The upper small intestine is unexpectedly rich in ghrelin cells, and these cells contribute to circulating ghrelin. Ghrelin and motilin are co-produced in the same cells in the duodenum and jejunum of both species, and ghrelin and motilin are stored in all secretory granules of such cells in humans, indicating co-secretion. The plasma profiles of ghrelin and motilin in pig were parallel and a correlation between ghrelin and motilin (r²=0.22; p<0.001) was evident in intestinal blood.

Conclusions: The upper small intestine is an important source of ghrelin. The likely co-secretion of intestinal ghrelin and motilin suggests concerted actions of the two hormones. These data may have implications for understanding gut motility and clinical implications for dysmotility and bariatric surgery.