Growth hormone-releasing peptide-2 reduces inward rectifying K+ currents via a PKA-cAMP-mediated signalling pathway in ovine somatotropes.
Xu. Ruwei R; Zhao. Yufeng Y; Chen. Chen C
Key Findings
- GHRP‑2 (100 nM) quickly and reversibly reduces Kir currents in ovine somatotropes.
- The reduction depends on the PKA‑cAMP signaling cascade; inhibitors of PKA or cAMP prevent the effect.
- PKC inhibition does not affect GHRP‑2’s action, indicating a PKC‑independent mechanism.
Practical Outcomes
- For biohackers using GHRP‑2 to boost growth hormone, this study suggests the peptide works through PKA activation rather than PKC, which may influence how you combine it with other supplements that affect cAMP/PKA (e.g., certain adaptogens or phosphodiesterase inhibitors). While the work is in sheep cells and not directly translatable to dosing in humans, it supports the idea that enhancing PKA signaling could amplify GHRP‑2’s GH‑releasing effects.
Summary
In sheep pituitary cells that make growth hormone, the peptide GHRP‑2 lowers a specific potassium current (Kir) by activating the PKA‑cAMP pathway, which makes the cells more electrically active and helps release growth hormone. This effect is blocked if PKA is inhibited, but not by blocking PKC.
Abstract
Inward-rectifying potassium (Kir) channels are essential for maintaining the resting membrane potential near the K(+) equilibrium and they are responsible for hyperpolarisation-induced K(+) influx. We characterised the Kir current in primary cultured ovine somatotropes and examined the effect of growth hormone-releasing peptide-2 (GHRP-2) on this current and its related intracellular signalling pathways. The Kir current was, in most cases, isolated using nystatin-perforated patch-clamp techniques. In bath solution containing 5 mM K(+), the Kir current was composed of both transient (fast activated) and delayed (slowly activated) components. An increase in the external K(+) concentration from 5 to 25 mM induced an augmentation of approximately 4-fold in the delayed part of the Kir current and both BaCl(2) and CsCl dose-dependently inhibited this current, confirming the presence of the Kir current in ovine somatotropes. Moreover, this specific effect of high K(+) on the Kir current was only observed in the cells that showed positive staining with anti-growth hormone (GH) antibodies, or in GC cells that belong to a rat somatotrope cell line. Application of GHRP-2 (100 nM) reversibly and significantly reduced the Kir current in bath solutions with 5 or 25 mM K(+) in ovine somatotropes. In addition, we found that the reduction in the Kir current mediated by GHRP-2 was totally abolished by the pretreatments with H89 (1 microM) or Rp-cAMP (100 microM) or by intracellular dialysis of a specific protein kinase A (PKA) inhibitory peptide PKI (10 microM). The specific PKC blocker chelerythrine (1 microM) or inhibitory peptide PKC(19-36) (10 microM) did not show any effects on the GHRP-2-induced decrease in the Kir current. These results suggest that the inhibition of Kir current through PKA-cAMP pathways may play an integral role in GHRP-2-induced depolarisation and GH release in ovine somatotropes.
Study Information
pubmed
2002
2002-12-01T00:00:00.000Z
10.1113/jphysiol.2002.030916
19
52