A lab study on sheep pituitary cells found that treating them with the peptide GHRP-2 for two days makes the cells fire more electrical signals and boosts certain potassium channels. This effect needs a specific cell‑signaling pathway (PKC) and new protein production. The changes could help the cells respond better to the body’s own growth‑hormone‑releasing signals.

Long-term in vivo treatment with synthetic GH-releasing peptides (GHRPs) enhances the release of GH induced by endogenous GHRH. The mechanism for such an enhancement on GH release is unknown. In this experiment, somatotropes were obtained from ovine pituitaries by enzyme dissociation and enriched by density centrifugation. Membrane voltage and currents were recorded with whole-cell patch-clamp configuration. After 48-h treatment with GHRP-2 (10(-8) M), the percentage of cells with spontaneous action potential was increased (51 vs. 27%) without change of resting potential. This GHRP-2 treatment also increased the amplitude of voltage-gated K+ currents (predominantly transient A-type-like current but also delayed rectifier or K-type-like current) without modification of biophysical kinetics. Down-regulation of protein kinase C (PKC) with phorbol 12-myristate 13-acetate at the time of adding GHRP-2 blocked the increase in K+ currents. Inclusion of calphostin C (PKC inhibitor) but not H(89) (protein kinase A inhibitor) significantly reduced the increase in K+ currents by GHRP-2. Inclusion of actinomycin D (transcription inhibitor) or cycloheximide (protein synthesis inhibitor) abolished the increase in K+ currents. These data indicate that 48-h GHRP-2 treatment increases the density of K+ channels via PKC and channel protein synthesis. Such a modification on K+ channels by GHRP-2 may be partially responsible for the change of somatotrope electrophysiological properties and sensitivity to GHRH stimulation.