Preprotachykinin A gene expression in distinct hypothalamic and brain stem regions of the rat is affected by a chronic osmotic stimulus: a combined immunohistochemical and in situ hybridization histochemistry study

Chronic osmotic stimulation influences the hypothalamoadenohypophysial axis by inhibiting the synthesis of corticotrophin releasing factor (CRF-41) in the parvocellular subdivision of the paraventricular nucleus (PVN) and, subsequently, the secretion of adrenocorticotrophin (ACTH) from the adenohypophysis. Using quantitative in situ hybridization histochemistry, we have investigated the effect of chronic osmotic stimulation on preprotachykinin A (PPT-A) mRNA levels in a number of brain areas known to send substance P-containing projections to the medial parvocellular part of the PVN. Chronic osmotic stimulation increased PPT-A gene expression in the lateral hypothalamic area, the arcuate nucleus, the catecholaminergic brain stem areas A2, Cl, and C2, although PPT-A mRNA levels in the bed nucleus of the stria terminalis, the medial preoptic nucleus, the caudate-putamen, and the Al were unaffected by chronic osmotic stimulation. In addition, immunohistochemical staining of substance P-immunoreactive elements contained within the same areas was carried out on colchicine-treated animals. Generally, those areas responding to the osmotic stimulus with increased PPT-A mRNA synthesis showed increased numbers of substance P-immunoreactive perikarya, suggesting that increased levels of mRNA are associated with increased peptide synthesis. These results provide evidence that central endogenous substance P contained in brain regions projecting to the paraventricular nucleus could have an inhibitory influence over the synthesis of CRF-41 during a chronic osmotic stimulus.