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 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.
Boehm
S
S
Department of Neuropharmacology, University of Vienna, Austria.
Huck
S
S
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D000068438:Brimonidine Tartrate; D002478:Cells, Cultured; D002642:Chick Embryo; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005728:Ganglia, Sympathetic / Q000502:physiology*; D006727:Hormone Antagonists / Q000494:pharmacology; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010456:Peptides, Cyclic / Q000494:pharmacology; D037342:Pertussis Toxin; D011810:Quinoxalines / Q000494:pharmacology; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects / Q000502:physiology*; D017481:Receptors, Somatostatin / Q000187:drug effects / Q000502:physiology*; D013004:Somatostatin / Q000494:pharmacology*; D053561:Somatostatin-28; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D000316:Adrenergic alpha-Agonists; D006727:Hormone Antagonists; D010456:Peptides, Cyclic; D011810:Quinoxalines; D018341:Receptors, Adrenergic, alpha-2; D017481:Receptors, Somatostatin; D010566:Virulence Factors, Bordetella; D000068438:Brimonidine Tartrate; D013004:Somatostatin; C040968:seglitide; D053561:Somatostatin-28; D037342:Pertussis Toxin; D009638:Norepinephrine