title: Somatostatin increases voltage-gated K+ currents in GH3 cells through activation of multiple somatostatin receptors.
abstract: The secretion of GH by somatotropes is inhibited by somatostatin (SRIF) through five specific membrane receptors (SSTRs). SRIF increases both transient outward (IA) and delayed rectifying (IK) K+ currents. We aim to clarify the subtype(s) of SSTRs involved in K+ current enhancement in GH3 somatotrope cells using specific SSTR subtype agonists. Expression of all five SSTRs was confirmed in GH3 cells by RT-PCR. Nystatin-perforated patch clamp was used to record voltage-gated K+ currents. We first established the presence of IA and IK type K+ currents in GH3 cells using different holding potentials (-40 or -70 mV) and specific blockers (4-aminopirimidine and tetraethylammonium chloride). SRIF (200 nM) increased the amplitude of both IA and IK in a fully reversible manner. Various concentrations of each specific SRTR agonist were tested on K+ currents to find the maximal effective concentration. Activation of SSTR2 and SSTR4 by their respective agonists, L-779,976 and L-803,087 (10 nM), increased K+ current amplitude without preference to IA or IK, and abolished any further increase by SRIF. Activation of SSTR1 and SSTR5 by their respective agonists, L-797,591 or L-817,818 (10 nM), increased K+ current amplitude, but SRIF evoked a further increase. The SSTR3 agonist L-797,778 (10 nM) did not affect the K+ currents or the response to SRIF. These results indicate that SSTR1, -2, -4, and -5 may all be involved in the enhancement of K+ currents by SRIF but that only the activation of SSTR2 or -4 results in the full activation of K+ current caused by SRIF.
authors.affiliation: Prince Henry's Institute of Medical Research, Monash University, Melbourne, Australia.
authors.forename: Seung-Kwon
authors.initials: SK
authors.lastname: Yang
authors.forename: Helena C
authors.initials: HC
authors.lastname: Parkington
authors.forename: Allan D
authors.initials: AD
authors.lastname: Blake
authors.forename: Damien J
authors.initials: DJ
authors.lastname: Keating
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
mesh_terms: D000818:Animals; D002460:Cell Line; D013006:Growth Hormone / Q000378:metabolism*; D006728:Hormones / Q000494:pharmacology*; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated / Q000187:drug effects* / Q000502:physiology*; D020033:Protein Isoforms / Q000819:agonists / Q000378:metabolism; D051381:Rats; D017481:Receptors, Somatostatin / Q000819:agonists / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013004:Somatostatin / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D006728:Hormones; D024642:Potassium Channels, Voltage-Gated; D020033:Protein Isoforms; D017481:Receptors, Somatostatin; D013004:Somatostatin; D013006:Growth Hormone