Author/Editor		Haellbrink, Mattias; Saar, Kuelliki; OEstenson, Claes-Goeran; Soomets, Ursel; Efendic, Suad; Howl, John; Wheatley, Mark; Zorko, Matjaž; Langel, UElo
Title		Effects of vasopressin-mastoparan chimeric peptides on insulin release and G-protein activity
Type		članek
Source		Regul Pept
Vol. and No.		Letnik 82
Publication year		1999
Volume		str. 45-51
Language		eng
Abstract		Two chimeric peptides, consisting of the linear vasopressin receptor V1 antagonist PhAc-D-Tyr(Me)-Phe-G1n-Asn-Arg-Pro-Arg-Tyr, in the N-terminus and mastoparan in the C-terminus connected directly (M375) or via 6-aminohexanoic acid (M391), have been synthesised. At 10 microM concentration, these novel peptides increased insulin secretion from isolated rat pancreatic islet cells 18-26-fold at 3.3 mM glucose and 3.5-5-fold at 16.7 mM glucose. PTX pretreatment of the islets decreased the peptide-induced insulin release. M375 and M391 bind to V1a vasopressin receptors with affinities lower than the unmodified vasopressin antagonist, but with KD values of 3.76 nM and 9.02 nM, respectively, both chimeras are high affinity ligands. The GTPase activity and GTPgamaS binding in the presence of these peptides has been characterised in Rin m5F cells. Comparison of the influence of the peptides M375 and M391 on GTPase activity in native and pertussis toxin-treated cells suggests a selective activation of Galfai/Galfao subunits, combined with a suppression of other GTPases, primarily Galfas. However, the GTPgamaS binding data show that the peptides retain some of the activating property even in PTX-treated cell membranes. In conclusion, the conjugation of mastoparan with the V1a, receptor antagonists produce peptides with properties different from the parent peptides that could be used to elucidate the role of different G proteins in insulin release.
Descriptors		INSULIN VASOPRESSINS CHIMERIC PROTEINS GTP PHOSPHOHYDROLASE GTP-BINDING PROTEINS RADIOMETRY ISLETS OF LANGERHANS