In a lab test using sheep pituitary cells, the peptide GHRP‑2 (also called KP 102) boosted growth‑hormone release as strongly as the classic growth‑hormone‑releasing factor (GRF) and was ten times more potent than older GHRP versions. The two peptides added together for an even bigger effect, and GHRP‑2’s action could be blocked by a GRF‑receptor antagonist, showing it works through a different receptor. The response needed calcium entry, but using GHRP‑2 didn’t make the cells less responsive to a later GRF dose.

A newly synthesised GH-releasing peptide, KP 102 (also named GHRP-2), was studied in an in vitro perifusion system of primary cultured ovine anterior pituitary cells. Application of KP 102 to the perifusion medium caused a dose-dependent increase in GH secretion. Dose-response relationships indicated that KP 102 had similar potency to GRF and was 10-fold more potent than earlier generations of GH-releasing peptide (GHRP-6 and GHRP-1) tested in same system. The response to a second application of KP 102 given within 1 h of initial application was significantly lower than the response to the first application. When KP 102 (or GRF) was applied first and then GRF (or KP 102) given 1 h later, the second response was not attenuated. When GRF and KP 102 were coadministered, an additive effect on release of GH was obtained. The effect of maximal dose of KP 102 (100 nM) on GH release was totally abolished by [Ac-Tyr1,D-Arg2] GRF 1-29 (1 microM) which is believed to be a specific antagonist for the GRF receptor. Blockade of Ca2+ channels by Cd2+ (2 mM) diminished the basal GH secretion and abolished the increase in GH release in response to KP 102 (100 nM). These data suggest that the action of KP 102 is blocked by a GRF receptor antagonist and therefore acts through a different receptor to that employed by earlier generations of GH-releasing peptides. GH release in response to KP 102 involves an increase in Ca2+ influx and there is no cross-desensitization between KP 102 and GRF responses.