A somatostatin receptor inhibits noradrenaline release from chick sympathetic neurons through pertussis toxin-sensitive mechanisms: comparison with the action of alpha 2-adrenoceptors

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 Ca2+ currents occurred at concentrations more than ten-fold higher than those required for the reduction of stimulation evoked 3H overflow. The action of somatostatin upon Ca2+ currents was also abolished by pertussis toxin and desensitized within minutes. In preceding experiments, alpha 2-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 alpha 2-adrenergic agonist UK 14,304 completely occluded the inhibition of Ca2+ 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 SRIF1 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 alpha 2-adrenergic agonists share all of these actions and occlude the effects of somatostatin, alpha 2-adrenoceptors and SRIF1 receptors seem to regulate sympathetic transmitter release via common signalling mechanisms.