A NEW BIOLOGICAL CONTRIBUTION OF CYCLO(HIS-PRO) TO THE PERIPHERAL INHIBITION OF PANCREATIC-SECRETION

The tripeptide pyro-Glu-His-Pro-NH2 [thyrotropin-releasing hormone (TR H)] was isolated from the hypothalamus as a thyrotropin-releasing fact or. It has a broad spectrum of central nervous system-mediated actions , including the stimulation of exocrine pancreatic secretion. TRH is a lso synthesized in the endocrine pancreas and found in the systemic ci rculation. Enzymatic degradation of TRH in vivo produces other bioacti ve peptides such as cyclo(His-Pro). Because of the short half-life of TRH and the stability of cyclo(His-Pro) in vivo, we postulated that at least part of the peripheral TRH effects on the exocrine pancreatic s ecretion may be attributed to cyclo(His-Pro), which has been shown to have other biological activities. This study determines in parallel th e peripheral effects of TRH and cyclo(His-Pro) as well as the putative contribution of other TRH-related peptides on exocrine pancreatic sec retion in rats. TRH and its metabolite cyclo(His-Pro) dose dependently inhibited 2-deoxy-D-glucose (2-DG)-stimulated pancreatic secretion. T RH and all the related peptides tested had no effect on the basal and cholecystokinin-stimulated amylase release from pancreatic acinar cell s in vitro. These data indicate that cyclo(His-Pro) mimics the periphe ral inhibitory effect of TRH on 2-DG-stimulated exocrine pancreatic se cretion. This effect is not detected on isolated pancreatic acini. Our findings provide a new biological contribution for cycle(His-Pro) wit h potential experimental and clinical applications.