Evidence for co‐transmitter role of neuropeptide Y in the pig spleen

Abstract

1 The possible involvement of neuropeptide Y (NPY) in relation to noradrenaline (NA) and adenosine triphosphate (ATP) mechanisms in the sympathetic nervous control of the vascular tone and capsule contraction in the blood perfused pig spleen was investigated in vivo. 2 Local injections or infusions of NA, NPY and a-, f-methylene ATP (mATP) caused vasonconstriction (perfusion pressure increase) and capsule contraction (increased venous blood flow). ATP only evoked vasodilatation. NPY was about 50 fold more potent than NA as a vasoconstrictor, and the NPY response was more long-lasting. Reserpine treatment did not change the effects of NPY. 3 Electrical stimulation of the splenic nerves in control animals caused a frequency-dependent, guanethidine-sensitive output of both NPY-like immunoreactivity (-LI) and NA, suggesting corelease. The output of NPY-LI relative to NA was enhanced at high frequency stimulation. Furthermore, a-adrenoceptor blockade by phentolamine enhanced both the output of NPY-LI and NA while inhibition of the neuronal uptake of NA with desipramine reduced the low frequency stimulation-evoked overflow of NPY-LI. Preganglionic denervation did not change the output of NPY-LI or NA. 4 Reserpine treatment reduced both the splenic content of NA and NPY-LI. Preganglionic denervation inhibited the reserpine-induced depletion of the NPY content but not of NA in terminal areas. The stimulation-evoked NPY overflow was markedly enhanced, especially at low-frequency stimulation after resperpine, and the plasma levels of NPY-LI in the venous effluent were then in the nmolar range (i.e. where exogenous NPY induced vasoconstriction). The perfusion-pressure increase upon stimulation in reserpine-treated, preganglionically-denervated animals was highly correlated (r = 0.91) to the NPY overflow. The functional 0.5 Hz responses were reduced after reserpine, while at higher frequencies the functional effects were of similar magnitude to controls but longer-lasting.5 Tyramine induced a release of NA but not of NPY-LI. Furthermore, the increase in perfusion pressure induced by tyramine was absent after reserpine.6 After tachyphylaxis to the vasoconstrictor effects of mATP, the nerve stimulation-evoked, functional response as well as the NA and NPY-LI overflow were unchanged. After reserpine treatment, both the perfusion-pressure increase and NPY-LI overflow to nerve stimulation were reduced after mATP tachyphylaxis. 7 In conclusion, release of NPY rather than ATP may explain the long-lasting, non-adrenergic, splenic functional responses in reserpinized animals upon sympathetic stimulation. However, NA is most likely the main splenic transmitter when low-frequency stimulation is used under control conditions. Neuropeptide Y (NPY), a peptide with 36 amino porcine brain (Tatemoto, 1982), co-exists with noracid residues which was originally isolated from adrenaline (NA) in postganglionic, sympathetic nerves in a variety of peripheral organs (Lundberg et

The actions of endothelins−1 and −3 on the vascular and capsular smooth muscle of the isolated blood perfused spleen of the dog

“…The present results therefore indicate that ET-1 is 4-5 times more potent, on a molar basis, as a splenic arterial vasoconstrictor than NPY, the co-transmitter in the sympathetic innervation (Lundberg et al, 1989). In addition, the splenic vasoconstrictor response to ET-1 is significantly longer in duration of action than an equieffective dose of NA.…”

Inhibition of sympathetic vasoconstriction in pigs in vivo by the neuropeptide Y‐Y1 receptor antagonist BIBP 3226

“…Unfortunately, in vivo desensitization with the Pa,, receptor agonist a,fl-methylene ATP has not yielded conclusive evidence for ATP being a sympathetic non-adrenergic transmitter in pig nasal mucosa or spleen (Lundberg et al, 1989c), even at single pulse stimulation (Lacroix et al, 1989). Experiments using selective purinoceptor antagonists, both in control and in reserpine-treated pigs, will be necessary to solve this issue.…”

Effect of lisinopril on tissue levels of neuropeptide Y in normotensive and spontaneously hypertensive rats

“…7 Despite evidence for NPY and NA acting as co-transmitters in the control of vascular resistance, 8 it is not known whether factors exerting a regulatory influence on sympathetic function alter the synthesis and release of these neurotransmitters in a differential or parallel manner. Here the effect of ACE inhibition with lisinopril on tissue levels of NPY and NA were studied in normotensive and spontaneously hypertensive rats (SHR).…”