TY - JOUR
T1 - Antagonism of VIP-stimulated cyclic AMP formation in chick brain
AU - Nowak, Jerzy Z.
AU - Sedkowska, Paulina
AU - Zawilska, Jolanta B.
AU - Gozes, Illana
AU - Brenneman, Douglas E.
N1 - Funding Information:
Part of the results described in this paper were presented at the Twelfth Annual Meeting of the European Neuropeptide Club (ENC) Neuropeptides 2002, From Molecule to Man (May 22–25, 2002, Olsztyn, Poland). The authors thank Katarzyna Kuba, M.Sc., for her technical help in some experiments. This research was supported by grant nos. 6P04C037-17 and 6P05A077-21 from the State Committee for Scientific Research (KBN) in Poland.
PY - 2003/4
Y1 - 2003/4
N2 - Of eight peptides tested (0.01-5 μM), only two, that is, pituitary adenylate cyclase-activating polypeptide (PACAP27) and chicken vasoactive intestinal peptide (cVIP), potently stimulated cyclic AMP (cAMP) production in cerebral cortical slices of the chick. Mammalian VIP (mVIP) showed some activity only at the highest dose tested, whereas truncated forms of PACAP or VIP, that is, PACAP6-27, cVIP6-28, and mVIP6-28, or hybrid compounds, that is, neurotensin6-11-cVIP7-28 (NT-cVIP) and neurotensin6-11-mVIP7-28 (NT-mVIP), were inactive. Thirty-minute preincubation of chick cortical slices with 5 μM PACAP6-27, NT-cVIP, or NT-mVIP competitively antagonized the cAMP effects of cVIP (0.03-1μM), with the truncated form of PACAP being the best antagonist. Preincubation of slices with 5 μM mVIP6-28 also produced a significant inhibition of the cVIP (0.1-1 μM)-induced increase in cAMP production; however its action was independent of the concentration of cVIP. In contrast to mVIP6-28, cVIP6-28 showed no antagonistic activity against the full-length peptide. In parallel experiments, 30-min pretreatment of cortical slices with 5 μM PACAP6-27 significantly antagonized the PACAP38-evoked increase in cAMP formation, whereas mVIP6-28 or the NT-mVIP hybrid was ineffective. It has been concluded that in the chick brain, PACAP and cVIP stimulate cAMP biosynthesis via PAC1 and VPAC-type receptors, respectively, and PACAP6-27 seems to be the most potent, yet PACAP/VIP receptor-nonselective antagonist. Unlike truncated PACAP, the NT-VIP hybrid peptides tested may represent VPAC-type receptor-selective blocking activity.
AB - Of eight peptides tested (0.01-5 μM), only two, that is, pituitary adenylate cyclase-activating polypeptide (PACAP27) and chicken vasoactive intestinal peptide (cVIP), potently stimulated cyclic AMP (cAMP) production in cerebral cortical slices of the chick. Mammalian VIP (mVIP) showed some activity only at the highest dose tested, whereas truncated forms of PACAP or VIP, that is, PACAP6-27, cVIP6-28, and mVIP6-28, or hybrid compounds, that is, neurotensin6-11-cVIP7-28 (NT-cVIP) and neurotensin6-11-mVIP7-28 (NT-mVIP), were inactive. Thirty-minute preincubation of chick cortical slices with 5 μM PACAP6-27, NT-cVIP, or NT-mVIP competitively antagonized the cAMP effects of cVIP (0.03-1μM), with the truncated form of PACAP being the best antagonist. Preincubation of slices with 5 μM mVIP6-28 also produced a significant inhibition of the cVIP (0.1-1 μM)-induced increase in cAMP production; however its action was independent of the concentration of cVIP. In contrast to mVIP6-28, cVIP6-28 showed no antagonistic activity against the full-length peptide. In parallel experiments, 30-min pretreatment of cortical slices with 5 μM PACAP6-27 significantly antagonized the PACAP38-evoked increase in cAMP formation, whereas mVIP6-28 or the NT-mVIP hybrid was ineffective. It has been concluded that in the chick brain, PACAP and cVIP stimulate cAMP biosynthesis via PAC1 and VPAC-type receptors, respectively, and PACAP6-27 seems to be the most potent, yet PACAP/VIP receptor-nonselective antagonist. Unlike truncated PACAP, the NT-VIP hybrid peptides tested may represent VPAC-type receptor-selective blocking activity.
KW - Chick cerebral cortex
KW - Cyclic AMP (cAMP)
KW - PACAP
KW - PACAP antagonist
KW - VIP
KW - VIP antagonist
UR - http://www.scopus.com/inward/record.url?scp=0037942717&partnerID=8YFLogxK
U2 - 10.1385/JMN:20:2:163
DO - 10.1385/JMN:20:2:163
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AN - SCOPUS:0037942717
SN - 0895-8696
VL - 20
SP - 163
EP - 171
JO - Journal of Molecular Neuroscience
JF - Journal of Molecular Neuroscience
IS - 2
ER -