title: Nerve activity-dependent variations in clearance of released noradrenaline: regulatory roles for sympathetic neuromuscular transmission in rat tail artery.
abstract: The aim of this study was to find out if clearance of noradrenaline released from sympathetic nerve terminals in rat isolated tail artery is a physiological variable and if so, to determine its role for the noradrenaline-mediated neurogenic contraction. The per pulse release of noradrenaline induced by electrical nerve stimulation and the fluctuations of the level of noradrenaline at the receptors driving the contractions were assessed from the electrochemically determined noradrenaline oxidation current at a carbon fibre electrode at the surface of the artery. Both were compared with the noradrenaline-mediated neurogenic contraction. The effects on these parameters of cocaine or desipramine, or of corticosterone, were used to assess the relative roles of neuronal and extraneuronal uptake, respectively. The effects of cocaine or desipramine, which enhance the noradrenaline level at the receptors by blocking neuronal reuptake, were compared with those of yohimbine, presumed to act exclusively by enhancing the per pulse release of noradrenaline. The results seem to support the following tentative conclusions. Clearance of released noradrenaline occurs by neuronal uptake and diffusion, while extraneuronal uptake is negligible. The noradrenaline-induced neurogenic contraction is mediated via adrenoceptors on cells near the plane of the nerve plexus; the excitation spreads from these cells throughout the syncytium. The contractile response to exogenous noradrenaline may also be mediated via receptors on the innervated key cells. Reuptake of noradrenaline into the releasing varicosities, i.e. in "active junctions", is highly efficient for single quanta but rapidly saturated by repeated release, while reuptake of noradrenaline in the "surround" of active junctions is probably rarely saturated and more independent of nerve activity. Saturation of the transporter by repeated release of quanta from the same varicosity and the consequent accumulation of "residual" noradrenaline and increased diffusion out of the junction and recruitment of noradrenaline receptors in the surround may be the cause of the rapid growth of the contraction during a high frequency train. Diffusion of released noradrenaline away from the postjunctional receptors is restricted by a local nerve activity-dependent buffering mechanism which, in spite of fading of the per pulse release, helps maintain the noradrenaline concentration at the receptors and the contraction during long high-frequency trains. Reactivation of the clearance mechanisms upon cessation of nerve activity accelerates the relaxation.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: Department of Physiology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: L
authors.initials: L
authors.lastname: Stjärne
authors.forename: J X
authors.initials: JX
authors.lastname: Bao
authors.forename: F
authors.initials: F
authors.lastname: Gonon
authors.forename: M
authors.initials: M
authors.lastname: Msghina
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000294:innervation; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008297:Male; D009469:Neuromuscular Junction / Q000502:physiology*; D009474:Neurons / Q000378:metabolism; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000493:pharmacokinetics; D051381:Rats; D011919:Rats, Inbred Strains; D013564:Sympathetic Nervous System / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*; D013623:Tail / Q000098:blood supply*; D014661:Vasoconstriction / Q000502:physiology
chemical_list: D000317:Adrenergic alpha-Antagonists; D009638:Norepinephrine