Actions of neuropeptide Y on the rat adrenal cortex

Although several studies have demonstrated the presence of neuropeptide Y ( NPY) in nerves supplying the mammalian adrenal cortex, its function in this tissue remains unclear, with reports of both stimulatory and inhibitory ef fects on aldosterone secretion apparently depending on the tissue preparati on used. In the present study the effects of NPY on rat adrenal capsular ti ssue were investigated. NPY significantly stimulated aldosterone secretion in a dose-dependent manner, and this effect was abolished by atenolol, a be ta(1)-adrenergic antagonist. NPY also stimulated the release of catecholami nes from intact rat adrenal capsular tissue with the same dose-dependent re lationship as the stimulation of aldosterone release. These observations su ggest that the actions of NPY may be mediated by the local release of catec holamines from chromaffin cells within adrenal capsular tissue, as we have previously described for vasoactive intestinal peptide. The second part of this study concerned the NPY receptor subtype mediating the actions of NPY on the adrenal cortex. It was found that peptide YY stim ulated aldosterone release with a comparable potency to NPY, whereas pancre atic polypeptide (PP) was without effect. The Y-1 selective NPY analog Leu( 31)Pro(34)NPY had greater effect on aldosterone release than the Y-2 select ive analog NPY18-36. Studies using the specific Y-1 receptor antagonist BIB P 3226 showed significant attenuation of the aldosterone response to NPY, b ut no effect on the response to added norepinephrine. Binding studies carri ed out using [I-125] Npy revealed the presence of a single population of NP Y-binding sites with a K-d of 12.25 nmol/liter and a binding capacity of 62 3 fmol/mg protein. Competition studies revealed displacement of [I-125]Npy specific binding by NPY, peptide YY, and Leu(31)Pro(34)NPY, but not by othe r peptides. Messenger RNA analysis revealed the presence of messenger RNA c oding for both the Y-1 receptor and the Y-4 receptor, but not the other sub types. Taken together these data suggest that the effects of NPY on the rat adrenal cortex are mediated by the Y-1 receptor subtype.