Pharmacological characterization of neuropeptide Y and noradrenaline mechanisms in sympathetic control of pig spleen.
The mechanisms underlying the functional effects of neuropeptide Y (NPY)-like immunoreactivity (LI) and noradrenaline (NA) and their release evoked by nerve stimulation were studied with the blood-perfused pig spleen in vivo. Infusion of selective agonists and antagonists suggested the presence of alpha 1- and beta 2-adrenoceptors mediating vasoconstriction and vasodilatation, respectively. NPY caused a slight inhibition of stimulation-evoked [3H]NA release and a clearcut non-adrenergic vasoconstriction. Local pretreatment with phentolamine and prazosin as well as with clonidine and UK 14304 reduced the perfusion pressure response to nerve stimulation. Phentolamine, yohimbine and idazoxan enhanced while clonidine and UK 14304 decreased the output of [3H]NA or NA and NPY-LI. The subsequent addition of propranolol to the alpha-adrenoceptor antagonists was followed by reappearance at a considerable portion of the perfusion pressure response while the output of [3H]NA or NA and NPY-LI was slightly reduced. It is concluded that NPY exerts pre- and post-junctional actions in pig spleen that regulate both NA release and vascular tone. alpha 1-Adrenoceptors are mainly involved in vasoconstriction, and prejunctional alpha 2 mechanisms inhibit both NA and NPY release at a low frequency of stimulation. beta 2-Adrenoceptors mediate vasodilatation when NA release is enhanced with a minor effect on mediator secretion.
Lundberg
J M
JM
Department of Pharmacology, Karolinska Institute, Stockholm, Sweden.
Rudehill
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A
Sollevi
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D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004558:Electric Stimulation; D066298:In Vitro Techniques; D009478:Neuropeptide Y / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology*; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011941:Receptors, Adrenergic / Q000187:drug effects; D012039:Regional Blood Flow / Q000187:drug effects; D013154:Spleen / Q000098:blood supply / Q000187:drug effects / Q000294:innervation*; D013552:Swine; D013564:Sympathetic Nervous System / Q000187:drug effects*; D015016:Yohimbine / Q000494:pharmacology
D009478:Neuropeptide Y; D011941:Receptors, Adrenergic; D015016:Yohimbine; D011433:Propranolol; D009638:Norepinephrine; D010646:Phentolamine