Expression and electrophysiological studies of secretin in the rat hypothalamic paraventricular nucleus

Abstract

Secretin, a 27-amino-acid brain-gut hormone, is a putative neuropeptide believed to have neuromodulatory effects in the central nervous system (CNS). Secretin and its receptor are widely distributed in the CNS, including the hypothalamus. By using double immunofluorosence, we discovered that secretin and its receptor are expressed and colocalized with vasopressin (VP) and less with oxytocin (OT), two neurosecretory hormones synthesized in the hypothalamic paraventricular nucleus magnocellular (mgPVN) neurons. This observation suggested that secretin may modulate the activity of mgPVN neurons. Using whole-cell patch clamp on rat hypothalamic slices, we examined the effects of secretin in the electrophysiologically identified magnocellular neurons. Voltage-clamp studies indicated that 100nM secretin did not significantly affect the frequency of miniature inhibitory postsynaptic currents (control:2.9±1.1Hz; secretin:3.3±1.2Hz, n=5, p>0.05) and miniature excitatory postsynaptic currents (control:1.3±0.4Hz; secretin:1.3±0.6Hz, n=3, p>0.05). Their amplitudes were also unaltered. Current-clamp studies showed that membrane potential was unaffected by 30nM (control:­43.4±1.6mV; secretin:­44.3±1.4mV, n=3, p>0.05) and 100nM secretin (control:­42.4±0.5mV; secretin:­42.5±0.5mV, n=11, p>0.05). Our data demonstrated that secretin has no observable pre- and postsynaptic effects on mgPVN neurons despite the expression of secretin and its receptor in VP and OT cells. These results suggested that secretin may be stored in the mgPVN neurons and co-release with VP or OT to the posterior pituitary. Further investigation is necessary to substantiate this hypothesis and to understand the function of secretin receptors in the PVN.