Neuropeptide Y acts at an atypical receptor to evoke cardiovascular depression and to inhibit glutamate responsiveness in the brainstem.

Microinjection of neuropeptide Y (NPY) into the nucleus tractus solitarius (NTS) induces an initial and reversible fall in arterial pressure (AP) and heart rate (HR), along with a delayed and long-lasting blockade of cardiovascular responses to L-glutamate (L-Glu) injected into the same site and an inhibition of the baroreflex arc. By injecting NPY-receptor subtype selective agonists and NPY-related peptides into NTS we have sought to characterize the receptors that mediate these responses. Unilateral injections into NTS (9-90 pmol) of NPY as well as the Y1 receptor selective agonist [34Pro]NPY and the Y2 receptor selective fragment NPY 13-36 evoked comparable dose-dependent falls of AP and HR in the anesthetized and paralyzed rat. Injections into NTS of peptide YY or pancreatic polypeptide had no effect. Preinjection of NPY, [34Pro]NPY, NPY 13-36 (all at 90 pmol) as well as norepinephrine (6.7 nmol) virtually abolished the fall in AP and HR evoked by subsequent injections of L-Glu into NTS. Injection of peptide YY or pancreatic polypeptide (both at 90 pmol) did not affect the cardiovascular responses evoked by L-Glu in NTS. Injection of NPY (90 pmol) into the caudal ventrolateral medulla induced a slight fall in AP of -17 +/- 5 mm Hg (P less than .05) and a sustained fall in HR of -44 +/- 8 beats per min (P less than .01). Injection of NPY also abolished the fall in HR and AP evoked by L-Glu in the caudal ventrolateral medulla. The profile of the cardiovascular effects elicited by the NPY-related peptides in NTS does not correspond to either of the Y1 or the Y2 receptor subtypes. The findings suggest that NPY acts on an atypical receptor in NTS to lower AP and HR. Moreover, this receptor may also interfere with the L-Glu-evoked neurotransmission in the NTS. Finally, norepinephrine shared with NPY the ability to inhibit L-Glu-evoked responses in NTS; however, a much higher dose of norepinephrine (than NPY) was required.