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 α-adrenergic agonists and antagonists on ganglionic transmission and to determine if endogenously released norepinephrine contributed to synaptic depression. Significant regional differences in α adrenergic effects were observed. In neurons from ganglia of the head/neck region norepinephrine or selective α 2 agonists presynaptically inhibited ganglionic transmission and this effect was antagonized by the α 2 antagonist yohimbine. In the majority of cells membrane hyperpolarization accompanied presynaptic inhibition during superfusion of α 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 (≥ 3.5 h) also failed reduce PTD while neurons unresponsive to α 2 adrenoceptor agonists routinely exhibited PTD, implying the presence of other inhibitory neurotransmitters sharing a common presynaptic mechanism with α 2 agonists. In the majority of neurons from ganglia of the body region superfusion of norepinephrine or the selective α 1 agonist phenylephrine evoked membrane depolarization and facilitated ganglionic transmission. These effects were antagonized by the α 1 antagonist prazosin. The remaining neurons exhibited either α 2-mediated synaptic inhibition or no-response. In conclusion, inhibitory α 2 and excitatory α 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.