Evidence for Y1-receptor-mediated facilitatory, modulatory cotransmission by NPY in the rat anococcygeus muscle.

The potential role of neuropeptide Y (NPY) as a neuromodulatory cotransmitter was investigated in rat anococcygeus muscle. The effects of NPY on contraction to norepinephrine or adrenergic nerve stimulation and on relaxation to nonadrenergic, noncholinergic nerve stimulation were analyzed. Norepinephrine-induced contraction was enhanced by NPY (0.1 microM). The Y1 receptor antagonist BIBP 3226 (1 microM) completely reversed this effect. NPY (0.01 or 0.1 microM) increased contractions induced by electrical field stimulation of sympathetic nerves. This increase was reduced by BIBP 3226 (1 microM), indicating Y1 receptor involvement. NPY (13-36) a Y2 receptor agonist, at 0.1 microM but not 0.01 microM, caused an increase of the nerve-induced contraction, which was reversed by BIBP 3226 (1 microM), indicating no Y2 receptor involvement. BIBP 3226 (1-1 microM) produced a concentration-dependent attenuation of nerve-mediated but not norepinephrine-mediated contraction. The reduction in nonadrenergic, noncholinergic nerve-induced relaxation to nerve stimulation by NPY (0.1 microM) was not affected by BIBP 3226 (1 microM). It is concluded that 1) exogenous NPY increases excitatory nerve-induced contraction mainly via a Y1 receptor-mediated effect on smooth muscle with a small non-Y1 receptor component due to blocking inhibitory nitrergic nerves and 2) endogenous NPY is a modulatory cotransmitter, which facilitates the primarily noradrenergic contractile responses to sympathetic nerve stimulation via smooth muscle Y1 receptors.