Overview of GHRP-2 Mechanisms

Bovine studies have suggested that GHRP-2 peptide exhibits multifaceted impacts, but its main mechanism of action appears to involve the GHS-Rs. These receptors are naturally triggered by ghrelin and may be found in various parts of the nervous system and other tissues. In the nervous system, they are located in the hypothalamus and the pituitary, among other structures. When GHRP-2 appears to engage with GHS-Rs, it’s believed that a structural transformation might be triggered upon attachment, possibly initiating intracellular signaling networks primarily mediated through G-proteins. The release of Gαq/11, a component of the G-proteins, might commence, potentially setting off subsequent signaling sequences. Phospholipase C (PLC) may split phosphatidylinositol 4,5-bisphosphate (PIP2) into secondary signaling molecules, IP3 and DAG (diacylglycerol). IP3 is thought to prompt the release of calcium ions. In contrast, DAG may activate protein kinase C (PKC), potentially heightening the signaling pathway and possibly facilitating the secretion of growth hormone from pituitary cells. Moreover, this process may also involve the activation of cyclic AMP (cAMP), which plays a crucial role in cellular signaling. Increasing cAMP levels may further enhance the signaling cascade, potentially boosting GH synthesis.^(13)(14) Nevertheless, GHRP-2 appears to induce desensitization at these receptors immediately after exposure, potentially reducing sensitivity lasting a complete four hours before reversal.⁽⁵⁾

By apparently activating the GHS-Rs on other parts of the nervous system, GHRP-2 might trigger a series of cellular events leading to the enhanced synthesis of hunger-promoting neuropeptides, namely Neuropeptide Y (NPY) and Agouti-related peptide (AgRP). These peptides are thought to be integral to the regulation of energy balance and the control of appetite. At the same time, GHRP-2 is believed to possibly inhibit the secretion of the appetite-reducing hormone, melanocyte-stimulating hormone (α-MSH), thus shifting the equilibrium towards increased hunger and encouraging dietary intake. Moreover, GHRP-2 might affect the mesolimbic reward system, a neural pathway associated with regulating the craving for food, via the activation of GHSR-1a receptors. This action might theoretically heighten the drive for food consumption, potentially through the activation of cyclic adenosine monophosphate (cAMP) pathways, further implicating GHRP-2 in the modulation of feeding behavior and reward-based eating.