Elsevier

Neuroscience

Volume 73, Issue 2, July 1996, Pages 595-604
Neuroscience

A somatostatin receptor inhibits noradrenaline release from chick sympathetic neurons through pertussis toxin-sensitive mechanisms: comparison with the action of α2-adrenoceptors

https://doi.org/10.1016/0306-4522(96)00074-7Get rights and content

Abstract

The effects of somatostatin and analogues were investigated in cultures of chick sympathetic neurons. Electrically evoked tritium overflow from cultures labelled with [3H]noradrenaline was reduced by somatostatin-14 in a concentration-dependent manner, with half maximal effects at 0.3 nM and a maximum of 45% inhibition. Somatostatin-28 was equipotent to somatostatin-14 (half maximal concentration at 0.5 nM), and seglitide was less potent, the effects being half maximal at 4.2 nM. The inhibitory action of somatostatin-14 on stimulation-evoked overflow desensitized within minutes at 100 nM, but not at 10 nM, and was abolished by a pretreatment of neurons with pertussis toxin. All somatostatin analogues reduced voltage-activated Ca2+ currents recorded in the whole-cell configuration of the patch-clamp technique, with somatostatin-14 being equipotent to somatostatin-28, but more potent than seglitide. However, the inhibition of Cal + currents occurred at concentrations more than ten-fold higher than those required for the reduction of stimulation evoked3H overflow. The action of somatostatin upon Ca2+ currents was also abolished by pertussis toxin and desensitized within minutes. In preceding experiments, α2-adrenoceptor activation had been found to reduce transmitter release and Ca2+ currents of chick sympathetic neurons through a pertussis toxin-sensitive mechanism. In the present study, the α2-adrenergic agonist UK 14, 304 completely occluded the inhibition of Ca t+ currents and of electrically evoked overflow by somatostatin-14. Neither UK 14, 304 nor somatostatin affected the resting membrane potential or voltage-dependent K+ currents.

These results demonstrate that chick sympathetic neurons possess SRIF, type somatostatin receptors which control transmitter release. This effect is mediated by pertussis toxin-sensitive GTP binding proteins and apparently involves an inhibition of voltage-activated Ca2+ channels, but not a modulation of K+ channels. Since α2-adrenergic agonists share all of these actions and occlude the effects of somatostatin, α2-adrenoceptors and SRIF1, receptors seem to regulate sympathetic transmitter release via common signalling mechanisms.

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