title: Alpha-adrenergic modulation of synaptic transmission in rabbit pancreatic ganglia.
abstract: Pancreatic ganglia contain noradrenergic nerve terminals whose role in ganglionic transmission is unknown. Intracellular recordings from rabbit pancreatic neurons were used to study the effects of alpha-adrenergic agonists and antagonists on ganglionic transmission and to determine if endogenously released norepinephrine contributed to synaptic depression. Significant regional differences in alpha adrenergic effects were observed. In neurons from ganglia of the head/neck region norepinephrine or selective alpha(2) agonists presynaptically inhibited ganglionic transmission and this effect was antagonized by the alpha(2) antagonist yohimbine. In the majority of cells membrane hyperpolarization accompanied presynaptic inhibition during superfusion of alpha(2) agonists. Repetitive nerve stimulation evoked a presynaptic post-train depression (PTD) of ganglionic transmission in all neurons tested. A combination of nisoxetine (selective inhibitor of the norepinephrine transporter) and tyramine (releaser of endogenous catecholamines) increased PTD. Pretreatment with clonidine inhibited synaptic transmission and abolished PTD while yohimbine did not affect it. Pretreatment with guanethidine (>or=3.5 h) also failed reduce PTD while neurons unresponsive to alpha(2) adrenoceptor agonists routinely exhibited PTD, implying the presence of other inhibitory neurotransmitters sharing a common presynaptic mechanism with alpha(2) agonists. In the majority of neurons from ganglia of the body region superfusion of norepinephrine or the selective alpha(1) agonist phenylephrine evoked membrane depolarization and facilitated ganglionic transmission. These effects were antagonized by the alpha(1) antagonist prazosin. The remaining neurons exhibited either alpha(2)-mediated synaptic inhibition or no-response. In conclusion, inhibitory alpha(2) and excitatory alpha(1) adrenoceptors exist in pancreatic ganglia and predominate in the head/neck and body, respectively. Norepinephrine, released during repetitive nerve stimulation, may contribute to synaptic depression in the head/neck region and appeared to share a common mechanism with other, unidentified neurotransmitters mediating synaptic depression in both regions. These differences indicate a functional heterogeneity of pancreatic sympathetic innervation that may reflect the reported regional differences in exocrine and endocrine cells.
authors.affiliation: Department of Pharmacology and Toxicology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216-4505, USA.
authors.forename: Eunyoung
authors.initials: E
authors.lastname: Yi
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Love
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D003000:Clonidine / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005260:Female; D005473:Fluoxetine / Q000031:analogs & derivatives / Q000494:pharmacology; D005725:Ganglia, Autonomic / Q000187:drug effects / Q000378:metabolism*; D006145:Guanethidine / Q000494:pharmacology; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000378:metabolism*; D010179:Pancreas / Q000187:drug effects / Q000294:innervation*; D010656:Phenylephrine / Q000494:pharmacology; D011817:Rabbits; D011941:Receptors, Adrenergic / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D000316:Adrenergic alpha-Agonists; D011941:Receptors, Adrenergic; D005473:Fluoxetine; C011386:nisoxetine; D010656:Phenylephrine; D015016:Yohimbine; D003000:Clonidine; D009638:Norepinephrine; D006145:Guanethidine