Outward current produced by somatostatin (SRIF) in rat anterior cingulate pyramidal cells in vitro.
1. A high density of receptors for somatostatin (SRIF) exists in the anterior cingulate cortex but their function is unknown. Whole-cell patch clamp recordings were made from visualized deep layer pyramidal cells of the rat anterior cingulate cortex contained in isolated brain slices to investigate the putative effects of SRIF and to identify the receptor subtype(s) involved. 2. SRIF (1-1000 nM) produced a concentration-dependent outward current which was associated with an increased membrane conductance, was sensitive to Ba2+ (300 microM - 1 mM), and was absent in the presence of a maximal concentration of the GABA(B) receptor agonist, baclofen (100 microM). These observations suggest the outward current was carried by K+ ions. 3. SRIF analogues also elicited outward currents with a rank potency order of (EC50, nM): octreotide (1.8)>BIM-23027 (3.7)>SRIF (20)=L-362,855 (20). BIM-23056 was without agonist or antagonist activity. Responses to L-362,855 were unlike those to the other agonists since they were sustained for the duration of the application. 4. The sst2 receptor antagonist, L-Tyr8Cyanamid 154806 (1 microM), had no effect alone but partially reversed responses to submaximal concentrations of SRIF (100 nM, 44+/-6% reversal) and L-362,855 (100 nM, 70+/-6% reversal) and fully reversed the response to BIM-23027 (10 nM). In contrast, L-Tyr8Cyanamid 154806 did not antagonize the response to baclofen (10 microM). 5. We conclude that SRIF activates a K+ conductance in anterior cingulate pyramidal neurones via an action predominantly at sst2 receptors.
Hicks
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Glaxo Institute of Applied Pharmacology, Department of Pharmacology, University of Cambridge.
Feniuk
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Humphrey
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D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D004347:Drug Interactions; D018755:GABA Agonists / Q000494:pharmacology; D006179:Gyrus Cinguli / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009842:Oligopeptides / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010456:Peptides, Cyclic / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors; D013004:Somatostatin / Q000494:pharmacology*
C091737:BIM 23056; D018755:GABA Agonists; C091739:L 362855; D009842:Oligopeptides; D010456:Peptides, Cyclic; D017481:Receptors, Somatostatin; D013004:Somatostatin; D001418:Baclofen