Modified GRF (1-29)

Mechanism (as reported)

A study in rat pancreatic plasma membranes reported that certain GRF analogs can interfere with vasoactive intestinal peptide (VIP) binding/inhibition and affect adenylate cyclase activity, with activity dependent on specific N-terminal and other positional changes in the analogs (PMID: 2859987). In a separate mast-cell study using human GRF(1-29)NH2, pertussis toxin inhibited histamine secretion, and the pathway sensitivity to cAMP modulation and protein kinase C (PKC) activation was investigated (PMID: 7544679). In a human physiology context, prior GHRH (GHRH 1-29) pretreatment was reported to abolish the GH response to a second GHRH bolus and also abolished pentagastrin-induced GH rise, suggesting hypothalamic-level regulation in that setting (PMID: 2071825). In rat GH response experiments, atropine reduced GH responses to GRF 1-29, supporting a role for cholinergic pathways in GH regulation in that experimental context (PMID: 9516049).

Key findings (each cites a source)

• A study reported that GRF and a panel of 14 GRF analogs (modified in the N-terminal part) inhibited [125I]iodo-VIP binding in rat pancreatic plasma membranes and that one peptide, (N-Ac-Tyr1,D-Phe2)-GRF(1-29)-NH2, selectively inhibited both VIP- and GRF-stimulated adenylate cyclase activities, consistent with interference at VIP-preferring receptors. [PMID 2859987]
• The same pancreatic-membrane study reported that alterations in positions 6 and 7 (but not positions 1-4) markedly reduced GRF analog affinity (based on Kact values) and that intrinsic adenylate cyclase activity was reduced by acetylation of a free NH2 group and by specific D-amino-acid substitutions (including Asp3, Ala4, Phe6, and Thr7). [PMID 2859987]
• A doping-material identification study reported that modified growth hormone releasing factor (modified GRF 1-29) was detected in seized powders and that the detected modification involved the addition of an extra glycine at the N-terminus. [PMID 30136411]
• A mast-cell activation study using human GRF(1-29)NH2 reported that histamine release from rat mast cells was non-cytotoxic and non-immunological, and that pretreatment with pertussis toxin markedly inhibited secretion, indicating involvement of a Gi-protein in the activation pathway as investigated. [PMID 7544679]
• In the same mast-cell study, IBMX was reported to inhibit mediator secretion while cholera toxin was reported to be ineffective in modifying histamine release, and PKC activation by TPA was reported to amplify the response to GRF(1-29)NH2. [PMID 7544679]
• A study in normal human subjects reported that prior administration of GHRH (GHRH 1-29) abolished the GH response to a second bolus of GHRH administered two hours later, and that pretreatment with GHRH also abolished the rise in GH induced by pentagastrin in the same experimental protocol. [PMID 2071825]
• A rat study reported that dopaminergic and alpha-adrenergic blockade did not affect GH responses to GRF 1-29, whereas prior administration of atropine reduced GH responses to GRF 1-29; the authors interpreted these findings as supporting a role for cholinergic pathways in regulation of GH secretion in that experimental context. [PMID 9516049]