Recent studies in our laboratory have demonstrated that rat platelets contain and release substances with neuropeptide Y-immunoreactivity (NPY- ir), which co-elute with authentic NPY in HPLC. We have discovered that platelets have specific, high-affinity NPY binding sites, and exogenous agents. These findings, along with the previously known cardiovascular actions of NPY (vasoconstriction & amplification of vasoconstrictor actions) have important implications in cardiovascular function during pathophysiological states involving platelet aggregation, and specifically with respect to platelet-vascular interactions. NPY, a 36-amino acid peptide, was previously known to be abundant in the brain, postganglionic, sympathetic noradrenergic nerves innervating the cardiovascular system, and catecholamine-containing chromaffin cells of the adrenal medulla. It is co-released with norepinephrine (NE) during sympathetic nerve stimulation and during prolonged and intense stress in animals and humans. Thus, there are at least two potential sources for circulating NPY: the sympatho- adrenomedullary system and platelets. Our overall hypothesis is that platelets are a major source of, and site of action for, neuropeptide Y (NPY), and that platelets derived NPY has important role in platelet- vascular interactions in pathophysiological states. This proposal will focus on the identification of platelet-derived NPY-ir and bioactivity, binding and second messenger systems of NPY in platelets, function of NPY in platelets, and defining whether platelet systems of NPY contributes to hemodynamic derangements in cardiovascular [pathophysiological models involving platelet activation. These objectives will be addressed in several experimental models previously used by the investigators in their studies on NPY, including in vitro studies of rat and human platelets, and in vivo rate hemodynamic models. Npy, if released by both sympathetic nerves and platelets during cardiovascular pathophysiological events may emerge as an important mediator of vascular-platelet interactions, with potential roles in shock, thrombosis, stroke and myocardial infraction.
| Myers, A K; Torres Duarte, A P; Zukowska-Grojec, Z (1993) Immunoreactive neuropeptide Y (NPY) in plasma and platelets of rat and mouse strains and human volunteers. Regul Pept 47:239-45 |
| Zukowska-Grojec, Z; Pruszczyk, P; Colton, C et al. (1993) Mitogenic effect of neuropeptide Y in rat vascular smooth muscle cells. Peptides 14:263-8 |
| Abi-Younes, S A; Ayers, M L; Myers, A K (1991) Mechanism of ethanol-induced aggregation in whole blood. Thromb Res 63:481-9 |
| Myers, A K; Abi-Younes, S; Zukowska-Grojec, Z (1991) Re-evaluation of the effects of neuropeptide Y on aggregation of human platelets. Life Sci 49:545-51 |
