Neuropeptide Y and noradrenaline mechanisms in relation to reserpine induced impairment of sympathetic neurotransmission in the cat spleen.
The mechanisms underlying the reserpine-induced impairment of the functional responses to sympathetic nerve stimulation and output of noradrenaline (NA) and neuropeptide Y (NPY)-like immunoreactivity (-LI) were studied using the isolated blood-perfused cat spleen. Splenic nerve stimulation (10 Hz for 2 min) during control conditions caused perfusion-pressure increase, volume reduction and an increased output of NA and NPY-LI. After administration of phenoxybenzamine, the nerve stimulation-induced perfusion-pressure increase was almost abolished, the volume reduction inhibited and the output of NPY-LI enhanced. After subsequent addition of propranolol, a clear-cut increase in perfusion pressure upon nerve stimulation reappeared. Local infusion of NPY caused a potent, long-lasting, adrenoceptor-resistant increase in perfusion pressure and a relatively smaller volume reduction of the spleen. Twenty-four hours after reserpine pretreatment (1 mg kg-1 i.v.), which depleted the splenic content of NA greater than 95% and NPY-LI by about 50%, the functional responses upon nerve stimulation were markedly reduced. Preganglionic denervation or pretreatment with the ganglionic-blocking agent chlorisondamine did not influence the NA depletion after reserpine treatment. A considerable, adrenoceptor antagonist-resistant, long-lasting functional response as well as a markedly enhanced output of NPY-LI then occurred upon nerve stimulation. In conclusion, reserpine treatment combined with interruption of preganglionic impulse flow reveals non-adrenergic, nerve stimulation evoked splenic functional responses which could be mediated by release of a cotransmitter peptide like NPY.
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002415:Cats; D004558:Electric Stimulation; D008297:Male; D009478:Neuropeptide Y / Q000008:administration & dosage / Q000493:pharmacokinetics*; D009638:Norepinephrine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012110:Reserpine / Q000494:pharmacology*; D013154:Spleen / Q000294:innervation*; D013564:Sympathetic Nervous System / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects*
D000317:Adrenergic alpha-Antagonists; D009478:Neuropeptide Y; D012110:Reserpine; D009638:Norepinephrine