Somatostatin increases voltage-gated K+ currents in GH3 cells through activation of multiple somatostatin receptors.
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.
Yang
Seung-Kwon
SK
Prince Henry's Institute of Medical Research, Monash University, Melbourne, Australia.
Parkington
Helena C
HC
Blake
Allan D
AD
Keating
Damien J
DJ
Chen
Chen
C
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
D006728:Hormones; D024642:Potassium Channels, Voltage-Gated; D020033:Protein Isoforms; D017481:Receptors, Somatostatin; D013004:Somatostatin; D013006:Growth Hormone