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Mod GRF 1-29

Sermorelin, Growth Hormone Releasing Hormone (1-29), hGRF(1-29)NH2

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Studies 227

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1996 pubmed 32 citations

Stable expression of the recombinant human VIP1 receptor in clonal Chinese hamster ovary cells: pharmacological, functional and molecular properties.

Gaudin. P P; Couvineau. A A; Maoret. J J JJ; Rouyer-Fessard. C C; Laburthe. M M

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Key Findings

VIP binds the VIP1 receptor with high affinity (Kd ≈ 0.4 nM) and strongly stimulates cAMP production (EC50 ≈ 0.2 nM).
The modified GRF‑1‑29 peptide ([Ac‑Tyr1,D‑Phe2]GRF‑(1‑29) amide) binds the VIP receptor with low affinity (Ki ≈ 1.6 µM) and does not trigger cAMP, acting instead as an antagonist.
Prolonged exposure to VIP causes the receptor to be internalized and its number (Bmax) to drop dramatically, reducing the cell’s response to the peptide.

Practical Outcomes

For biohackers using GRF‑1‑29 to boost growth hormone, this study suggests that at typical doses the peptide is unlikely to affect the VIP system, but very high concentrations could have off‑target antagonistic effects. It also highlights that chronic high‑dose VIP (or related peptides) can desensitize receptors, which may be relevant for dosing schedules of VIP‑like compounds.

Summary

Scientists made a stable cell line that shows how the human VIP1 receptor works. They measured how tightly VIP and similar peptides bind, how they trigger cAMP signals, and how the receptor behaves after long‑term exposure. One of the peptides tested was a modified version of GRF‑1‑29, which turned out to bind the VIP receptor only weakly and acted as an antagonist, not as an activator.

Abstract

We stably transfected Chinese hamster ovary (CHO) cells with the recombinant human vasoactive intestinal peptide (VIP)1 receptor. A clone referred to as Clone 15 was isolated and studied for receptor properties. The following data were obtained: (1) one class of binding site was identified by Scatchard analysis of [125I]VIP binding to cell membranes with a Kd of 0.41 nM and a Bmax of 1.62 pmol/mg protein; (2) the constant Ki for the inhibition of [125I]VIP binding by VIP and related peptides was: VIP (0.9 nM) = pituitary adenylate cyclase-activating peptide (PACAP)-27 (1.3 nM) < PACAP-38 (6.8 nM) < helodermin (46.0 nM) < human growth hormone-releasing factor (GRF) (0.6 microM) < peptide histidine methionineamide (2.0 microM) < secretin (> 10 microM); (3) cross-linking experiments using [125I]VIP identified a single M(r) 67000 recombinant receptor; (4) VIP stimulated cAMP production in Clone 15 cells with an EC50 of 0.20 nM; (5) some previously described VIP receptor antagonists including [4-Cl-D-Phe6, Leu17]VIP, [Ac-Tyr1,D-Phe2]GRF-(1-29) amide and VIP-(10-28) inhibited [125I]VIP binding with a Ki of 0.7, 1.6 and 2.5 microM, respectively. They failed to stimulate cAMP production in Clone 15 cells and inhibited, at least partially, the VIP (0.3 nM)-evoked cAMP production; (6) exposure of Clone 15 cells to 10 nM VIP for 24 h resulted in a sharp decrease in Bmax in Clone 15 cells (0.43 vs. 1.62 pmol/mg protein in control cells) and in the potency and efficacy of VIP in stimulating cAMP. Moreover, immunofluorescence studies using confocal microscopy indicated that the receptor was internalized and sequestered in vesicular structures within the cells. It is concluded that Clone 15 cells provide a valuable tool to further characterize various functional and pharmacological aspects of the human VIP1 receptor.

Study Information

Provider

pubmed

Year

1996

Date

1996-04-29T00:00:00.000Z

DOI

10.1016/0014-2999(96)00096-9

Citations

References