The evidence that MK-0677 is a functional mimetic of GHRP-6 is extensive and has been summarized by Patchett et al. (37,54) and Smith et al. (14). Neither increase cAMP in pituitary somatotrophs, although they synergize with GHRH to increase its GH secretion and cAMP elevation.Pituitary cell cultures become rapidly desensitized to both GHRP-6 and MK-0677 and cells desensitized to one are desensitized to the other. However, the MK-0677 desensitized cells have not been depleted of GH since they remain responsive to GHRH. Furthermore, the GH secretagogue activity of MK-0677 can be antagonized by the GHRP-6 antagonist His-D-Trp-D-Lys-Trp-D-Phe-Lys-NH2 MK-0677 and GHRP-6 share a common second messenger pathway in that both activate protein kinase C, produce a depolarization of somatotroph membranes and elevate intracellular Ca2+ levels. Neither alone affects the release of ACTH from pituitary cells. In summary, GHRP-6 and MK-0677 in all parameters tested behave functionally the same in rat pituitary cell culture.
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