A M Buchan1, P E Squires, M Ring, R M Meloche. 1. Department of Physiology, Faculty of Medicine, 2146 Health Sciences Mall, University of British Columbia, Vancouver V6T 1Z3, Canada. ambuchan@interchange.ubc.ca
Abstract
BACKGROUND AND AIMS: Human G cells express the calcium-sensing receptor and respond to extracellular calcium by releasing gastrin. However, the receptor on G cells is insensitive to serum calcium levels. We investigated whether this is a result of differential regulation of signaling pathways compared with parathyroid or calcitonin cells. METHODS: Gastrin release from primary cultures of human antral epithelial cells enriched for G cells (35%) was measured by radioimmunoassay. G cells were stimulated by increasing extracellular calcium concentration for 1 hour in the presence or absence of antagonists of specific intracellular signaling pathways. Intracellular calcium levels were monitored to evaluate the effect of the antagonists on calcium influx. RESULTS: Inhibition of phospholipase C decreased calcium-stimulated gastrin release, but blockers of adenylate cyclase, phospholipase A(2), or mitogen-activated protein kinase had no effect. Inhibition of protein kinase C, nonselective cation channels, and phosphodiesterase increased basal and calcium-stimulated gastrin release while decreasing calcium influx. These data were consistent with basally active phosphodiesterase. CONCLUSIONS: The calcium-sensing receptor on the G cell activates phospholipase C and opens nonselective cation channels, resulting in an influx of extracellular calcium. Protein kinase C isozymes expressed by the G cells play multiple roles regulating both gastrin secretion and phosphodiesterase activity.
BACKGROUND AND AIMS: Human G cells express the calcium-sensing receptor and respond to extracellular calcium by releasing gastrin. However, the receptor on G cells is insensitive to serum calcium levels. We investigated whether this is a result of differential regulation of signaling pathways compared with parathyroid or calcitonin cells. METHODS:Gastrin release from primary cultures of human antral epithelial cells enriched for G cells (35%) was measured by radioimmunoassay. G cells were stimulated by increasing extracellular calcium concentration for 1 hour in the presence or absence of antagonists of specific intracellular signaling pathways. Intracellular calcium levels were monitored to evaluate the effect of the antagonists on calcium influx. RESULTS: Inhibition of phospholipase C decreased calcium-stimulated gastrin release, but blockers of adenylate cyclase, phospholipase A(2), or mitogen-activated protein kinase had no effect. Inhibition of protein kinase C, nonselective cation channels, and phosphodiesterase increased basal and calcium-stimulated gastrin release while decreasing calcium influx. These data were consistent with basally active phosphodiesterase. CONCLUSIONS: The calcium-sensing receptor on the G cell activates phospholipase C and opens nonselective cation channels, resulting in an influx of extracellular calcium. Protein kinase C isozymes expressed by the G cells play multiple roles regulating both gastrin secretion and phosphodiesterase activity.
Authors: Yu Wang; Rashmi Chandra; Leigh Ann Samsa; Barry Gooch; Brian E Fee; J Michael Cook; Steven R Vigna; Augustus O Grant; Rodger A Liddle Journal: Am J Physiol Gastrointest Liver Physiol Date: 2010-12-23 Impact factor: 4.052
Authors: Jianying Feng; Clark D Petersen; David H Coy; Jian-Kang Jiang; Craig J Thomas; Martin R Pollak; Stephen A Wank Journal: Proc Natl Acad Sci U S A Date: 2010-09-27 Impact factor: 11.205