Differential effects of neuropeptide Y and opioids on neurogenic responses of the perfused rat mesentery

In perfused rat mesentery transmural nerve stimulation activates both adrenergic and capsaicin-sensitive sensory nerves. When adrenergic nerves were blocked with guanethidine and smooth muscle tone was increased, transmural nerve stimulation caused a dilator response which was attenuated by tetrodotoxin and abolished by capsaicin. Indomethacin increased the vasodilator response to transmural nerve stimulation, but did not affect the dilation to calcitonin gene-related peptide. Neuropeptide Y (NPY) potentiated vasoconstrictor responses to transmural nerve stimulation, but suppressed capsaicin-sensitive vasodilation, an effect which was unaltered by indomethacin. Opioid agonists selective for mu, delta or kappa receptors, DAMGO ([D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin), DPDPE ([D-Pen2,D-Pen5]enkephalin) and ethylketocyclazocine, had no effect on the vasoconstrictor response to transmural nerve stimulation. DAMGO and DPDPE significantly inhibited vasodilator responses to transmural nerve stimulation, but ethylketocyclazocine was without effect. After treatment with indomethacin, DAMGO still inhibited the vasodilator response, but DPDPE was no longer effective. Prejunctional control of transmitter release by NPY or opioids is dependent on the specific nerve type as well as, in some cases, the participation of endogenous prostaglandins.