Cellular actions of somatostatin on rat periaqueductal grey neurons in vitro.
Functional studies indicate that the midbrain periaqueductal grey (PAG) is involved in the analgesic actions of somatostatin; however, the cellular actions of somatostatin in this brain region are unknown. In the present study, whole-cell patch clamp recordings were made from rat PAG neurons in vitro. In 93% of acutely isolated neurons, somatostatin inhibited Ca(2+)-channel currents. This effect was mimicked by the sst-2 selective agonist BIM-23027, but not by the sst-1 and sst-5 selective agonists CH-275 and L-362855. In brain slices, 81% of neurons responded to somatostatin (300 nm) with an increase in K(+) conductance that reversed polarity at -114 mV. A greater proportion of somatostatin-sensitive neurons (93%) than somatostatin-insensitive neurons (53%) responded to the opioid agonist met-enkephalin (10 microm). Somatostatin also reduced the amplitude of evoked GABA(A)-mediated inhibitory postsynaptic currents (IPSCs). The actions of somatostatin in brain slices were mimicked by BIM-23027, but not by CH-275. Somatostatin had a variable effect on the rate of spontaneous miniature IPSCs in normal external potassium solutions. In high external potassium solutions, somatostatin reduced the rate of miniature IPSCs in all neurons, and this inhibition was abolished by addition of Cd(2+) (30 microm). Somatostatin had no effect on the amplitude of miniature IPSCs. These results indicate that somatostatin acts via sst-2 receptors to directly inhibit a subpopulation of PAG neurons by activating a potassium conductance and inhibits GABA release within PAG via a presynaptic Ca(2+)-dependent mechanism. Thus, like opioids, somatostatin has the potential to exert pre- and postsynaptic disinhibitory effects within the PAG.
Connor
Mark
M
Pain Management Research Institute, Northern Clinical School, University of Sydney, Royal North Shore Hospital, E25 NSW 2006, Australia.
Bagley
Elena E
EE
Mitchell
Vanessa A
VA
Ingram
Susan L
SL
Christie
MacDonald J
MJ
Humphrey
Patrick P A
PP
Vaughan
Christopher W
CW
D000818:Animals; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000166:cytology* / Q000187:drug effects* / Q000502:physiology; D010456:Peptides, Cyclic / Q000494:pharmacology; D010487:Periaqueductal Gray / Q000166:cytology* / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017481:Receptors, Somatostatin / Q000819:agonists / Q000378:metabolism; D013004:Somatostatin / Q000494:pharmacology*
C091738:BIM 23027; D010456:Peptides, Cyclic; D017481:Receptors, Somatostatin; D013004:Somatostatin; C093733:somatostatin receptor 2