BIBP-3226, SURAMIN AND PRAZOSIN IDENTIFY NEUROPEPTIDE-Y, ADENOSINE 5'-TRIPHOSPHATE AND NORADRENALINE AS SYMPATHETIC COTRANSMITTERS IN THE RAT ARTERIAL MESENTERIC BED

The physiological role of neuropeptide Y (NPY) and extracellular adeno sine 5'-triphosphate (ATP) in sympathetic neurotransmission is becomin g increasingly clear, To assess whether NPY and ATP act as cotransmitt ers together with noradrenaline (NA) in the sympathetic nerves of the superior mesenteric artery, the changes in perfusion pressure of the a rterial mesenteric bed caused by nerve stimulation were recorded, Depo larization of the perivascular superior mesenteric arterial nerves cau sed frequency-and time-dependent increases in the perfusion pressure t hat were abolished by guanethidine, which implied the sympathetic orig in of these responses. Independent perfusion with either 500 nM BIBP 3 226, an NPY Y-1 antagonist; 3 mu M suramin, a competitive purinoceptor antagonist; or 0.1 nM prazosin, a competitive alpha-1 adrenoceptor an tagonist, evoked approximately a 30% reduction in the rise in perfusio n pressure caused by the 20-to 30-Hz electrical depolarization of the perimesenteric arterial nerves, Prazosin (0.1 nM) blocked the increase s in perfusion pressure caused by electrical stimulation of the perime senteric nerves but did not significantly reduce the vasomotor effect of exogenous NA, Likewise, 5-methyl urapidil and chloroethylclonidine, alpha-1 adrenoceptor antagonists with selectivity for the alpha-1A an d alpha-1B receptor subtypes, respectively, concentration-dependently decreased the increase in perfusion pressure elicited by electrical st imulation of the perimesenteric nerves at concentrations lower than th at required to block the vasoconstriction elicited by exogenous NA. Th e combined perfusion of 3 mu M suramin plus 0.1 nM prazosin did not re sult in a complete inhibition of the physiological response. Only upon the simultaneous application of BIBP plus suramin plus prazosin was t he rise in perfusion pressure abolished. These results support the wor king hypothesis that the sympathetic nerves of the rat mesenteric bed release NPY, ATP and NA that act as postjunctional cotransmitters in t his neuroeffector junction.