The potential of secretin as neurohypophysial factor

Symposium 2 - Central mechanisms (1)Regulation of body fluid solute concentrations is critical to recovery from intracellular and extracellular dehydration. In either case, both physiological and behavioral responses, including release of the antidiuretic hormone vasopressin (VP) to prevent further water loss in the kidney and the dipsogenic peptide angiotensin II (ANGII) to increase fluid intake, are essential for constant body fluid content maintenance. Secretin is a classical gastrointestinal hormone that has recently been suggested to act as a neuropeptide in the central nervous system. The functions of secretin in renal water reabsorption have remained controversial until our recent data showing that secretin acts via a VP-independent mechanism to stimulate aquaporin-2 water channel surface presentation and expression in kidney tubules (1). Regarding the source of secretin, we provided evidence for secretin release from the posterior pituitary into circulation upon water deprivation or direct electrical stimulation of the PVN (2). In the hypothalamus, increased expressions of the secretin and its receptor are observed upon water deprivation (2). In addition, intracerebroventricular secretin injection revealed that secretin could stimulate VP expression in the hypothalamus and VP release into systemic circulation. More importantly, we found that the presence of a functional secretin and secretin receptor axis is essential to mediating the osmoregulatory effects of ANGII, hence, secretin is potentially the missing link that connects ANGII with its effects in the central nervous system (3). Taken together, secretin functions at multiple levels to regulate water balance in our body. It mediates the effects of central ANGII in higher brain centers, controls expressions and release of VP in the hypothalamo-pituitary axis, is released from posterior pituitary into circulation upon water deprivation, and activates aquaporin-2 expression and translocation in distal kidney tubules