Cholecystokinin B Receptor Gene Expression in Hypothalamic Neurosecretory Neurons after Experimental Manipulations

Magnocellular neurons of the supraoptic (SON) and paraventricular (PVN) nuclei projecting to the neurohypophysis produce, in addition to the classical hormones vasopressin and oxytocin, a large number of other peptides, one of which is cholecystokinin (CCK). Binding sites for CCK have been identified in the posterior pituitary. Recently the cDNAs for CCK_A and CCK_B receptors were isolated and characterized, and CCK_A and CCK_B receptor mRNAs were localized in the SON and PVN. We have used complementary oligonucleotides and in situ hybridization histochemistry to study CCK_B receptor mRNA in hypothalamic neurons. Changes in the expression of CCK_B receptor mRNA in the SON and PVN were analysed in salt-loaded as well as in hypophysectomized animals. Levels of CCK_B receptor mRNA in the PVN and SON increased markedly in salt-loaded animals as compared to controls. An increase in CCK_B receptor mRNA levels was seen in the SON and PVN after 3 days of salt loading, with high levels continuing through 5 and 7 days. At 14 days, the levels of CCK_Breceptor mRNA in the PVN were significantly lower as compared to 7 days. Hypophysectomy 5 days prior to sacrifice, resulting in a nerve lesion in the neurohypophysial pathway and removal of the anterior pituitary hormones, induced a significant increase in CCK_B receptor mRNA levels in neurons of the PVN. The increase in CCK_B receptor mRNA labelling after salt loading was mainly observed in the ventrolateral part of the PVN and in the dorsolateral part of the SON, corresponding to oxytocin-containing neurons, whereas the increase after hypophysectomy was mainly seen in the central part of the PVN and in the ventral part of the SON, corresonding to vasopressin-containing neurons. The results suggest that the synthesis of CCK_B receptors in magnocellular neurons is increased upon osmotic challenge and hypophysectomy.