Alpha-adrenergic modulation of synaptic transmission in rabbit pancreatic ganglia

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 α2 agonists presynaptically inhibited ganglionic transmission and this effect was antagonized by the α2 antagonist yohimbine. In the majority of cells membrane hyperpolarization accompanied presynaptic inhibition during superfusion of α2 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 α2 adrenoceptor agonists routinely exhibited PTD, implying the presence of other inhibitory neurotransmitters sharing a common presynaptic mechanism with α2 agonists. In the majority of neurons from ganglia of the body region superfusion of norepinephrine or the selective α1 agonist phenylephrine evoked membrane depolarization and facilitated ganglionic transmission. These effects were antagonized by the α1 antagonist prazosin. The remaining neurons exhibited either α2-mediated synaptic inhibition or no-response. In conclusion, inhibitory α2 and excitatory α1 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.