A SOMATOSTATIN RECEPTOR INHIBITS NORADRENALINE RELEASE FROM CHICK SYMPATHETIC NEURONS THROUGH PERTUSSIS-TOXIN-SENSITIVE MECHANISMS - COMPARISON WITH THE ACTION OF ALPHA(2)-ADRENOCEPTORS

The effects of somatostatin and analogues were investigated in culture s of chick sympathetic neurons. Electrically evoked tritium overflow f rom cultures labelled with [H-3]noradrenaline was reduced by somatosta tin-14 in a concentration-dependent manner, with half maximal effects at 0.3 nM and a maximum of 45% inhibition. Somatostatin-28 was equipot ent to somatostatin-14 (half maximal concentration at 0.5 nM), and seg litide was less potent, the effects being half maximal at 4.2 nM. The inhibitory action of somatostatin-14 on stimulation-evoked overflow de sensitized within minutes at 100 nM, but not at 10 nM, and was abolish ed by a pretreatment of neurons with pertussis toxin. All somatostatin analogues reduced voltage-activated Ca2+ currents recorded in the who le-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 sti mulation evoked H-3 overflow. The action of somatostatin upon Ca2+ cur rents was also abolished by pertussis toxin and desensitized within mi nutes. In preceding experiments, alpha(2)-adrenoceptor activation had been found to reduce transmitter release and Ca2+ currents of chick sy mpathetic neurons through a pertussis toxin-sensitive mechanism. In th e present study, the alpha(2)-adrenergic agonist UK 14,304 completely occluded the inhibition of Ca2+ currents and of electrically evoked ov erflow by somatostatin-14. Neither UK 14,304 nor somatostatin affected the resting membrane potential or voltage-dependent K+ currents. Thes e results demonstrate that chick sympathetic neurons possess SRIF(1) t ype somatostatin receptors which control transmitter release. This eff ect 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 agonist s share all of these actions and occlude the effects of somatostatin, alpha(2)-adrenoceptors and SRIF(1) receptors seem to regulate sympathe tic transmitter release via common signalling mechanisms. Copyright (C ) 1996 IBRO.