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Ghrelin and Motilin Are Cosecreted from a Prominent Endocrine Cell Population in the Small Intestine

Department of Experimental Medical Science (N.W., M.B., F.S.), Lund University, SE-22814 Lund, Sweden; Department of Cell and Organism Biology (B.W., S.P.), Lund University, SE-22362 Lund, Sweden; and Department of Internal Medicine (K.S.), Lund University Hospital, SE-22185 Lund, Sweden

Address all correspondence and requests for reprints to: Nils Wierup, Ph.D., Lund University, Department of Experimental Medical Science, Division of Diabetes, Metabolism, and Endocrinology, Unit of Neuroendocrine Cell Biology, BMC B11, SE-22 184 Lund, Sweden. E-mail: nils.wierup{at}med.lu.se.

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

Objective: The objective of the study was to perform a detailed mapping with specimens from all parts of the GI tract, and colocalization 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 hybridization, 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 coproduced 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 cosecretion. 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 cosecretion 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.