title: BIBP 3226, suramin and prazosin identify neuropeptide Y, adenosine 5'-triphosphate and noradrenaline as sympathetic cotransmitters in the rat arterial mesenteric bed.
abstract: The physiological role of neuropeptide Y (NPY) and extracellular adenosine 5'-triphosphate (ATP) in sympathetic neurotransmission is becoming increasingly clear. To assess whether NPY and ATP act as cotransmitters together with noradrenaline (NA) in the sympathetic nerves of the superior mesenteric artery, the changes in perfusion pressure of the arterial mesenteric bed caused by nerve stimulation were recorded. Depolarization of the perivascular superior mesenteric arterial nerves caused frequency- and time-dependent increases in the perfusion pressure that were abolished by guanethidine, which implied the sympathetic origin of these responses. Independent perfusion with either 500 nM BIBP 3226, an NPY Y1 antagonist; 3 microM suramin, a competitive purinoceptor antagonist; or 0.1 nM prazosin, a competitive alpha-1 adrenoceptor antagonist, evoked approximately a 30% reduction in the rise in perfusion pressure caused by the 20- to 30-Hz electrical depolarization of the perimesenteric arterial nerves. Prazosin (0.1 nM) blocked the increases in perfusion pressure caused by electrical stimulation of the perimesenteric 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 and alpha-1B receptor subtypes, respectively, concentration-dependently decreased the increase in perfusion pressure elicited by electrical stimulation of the perimesenteric nerves at concentrations lower than that required to block the vasoconstriction elicited by exogenous NA. The combined perfusion of 3 microM suramin plus 0.1 nM prazosin did not result in a complete inhibition of the physiological response. Only upon the simultaneous application of BIBP plus suramin plus prazosin was the rise in perfusion pressure abolished. These results support the working hypothesis that the sympathetic nerves of the rat mesenteric bed release NPY, ATP and NA that act as postjunctional cotransmitters in this neuroeffector junction.
authors.affiliation: Unidad de Regulación Neurohumoral, Departamento de Ciencias Fisiológicas, Facultad de Ciencias Biológicas, P. Universidad Catolica de Chile, Casilla, Santiago.
authors.forename: M V
authors.initials: MV
authors.lastname: Donoso
authors.forename: M
authors.initials: M
authors.lastname: Steiner
authors.forename: J P
authors.initials: JP
authors.lastname: Huidobro-Toro
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004558:Electric Stimulation; D008638:Mesenteric Arteries / Q000294:innervation / Q000378:metabolism*; D009478:Neuropeptide Y / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D011224:Prazosin / Q000494:pharmacology*; D058919:Purinergic P2 Receptor Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors; D013498:Suramin / Q000494:pharmacology*; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; C092926:BIBP 3226; D009478:Neuropeptide Y; D058919:Purinergic P2 Receptor Antagonists; D017476:Receptors, Neuropeptide Y; D013498:Suramin; D000255:Adenosine Triphosphate; D001120:Arginine; D009638:Norepinephrine; D011224:Prazosin