Primary structure of frog pituitary adenylate cyclase-activating polypeptide (PACAP) and effects of ovine PACAP on frog pituitary.
Pituitary adenylate cyclase-activating polypeptide (PACAP), a peptide of the glucagon-secretin-vasoactive intestinal polypeptide superfamily, was isolated in pure form from the brain of the European green frog, Rana ridibunda. The primary structure of the peptide indicates that evolutionary pressure to conserve the complete amino acid sequence has been very strong. Frog PACAP comprises 38 amino acid residues and contains only 1 substitution (isoleucine for valine at position 35) compared with human/ovine/rat PACAP. In the presence of the phosphodiesterase inhibitor isobutylmethylxanthine, synthetic ovine PACAP-(1-38) produced a dose-dependent increase in the concentration of cAMP in isolated frog anterior pituitary fragments (ED50 = 2.1 +/- 0.6 x 10(-7) M; mean +/- SE; n = 6). Maximum stimulation (an approximately 8-fold increase in concentration over basal values) was produced by 10(-6) M peptide. The truncated form of PACAP [PACAP-(1-27)] also produced a dose-dependent increase in cAMP in frog anterior pituitary fragments, and the potency of the peptide (ED50 = 5.9 +/- 0.6 x 10(-8) M) was comparable to that of PACAP-(1-38). The data suggest, therefore, that the function as well as the structure of PACAP have been conserved during the evolution of amphibia to mammals.
Chartrel
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European Institute for Peptide Research, Laboratory of Molecular Endocrinology, C.N.R.S. URA 650, INSERM, University of Rouen, Mont-Saint-Aignan, France.
Tonon
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MC
Vaudry
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Conlon
J M
JM
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D001923:Brain Chemistry; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D011895:Rana ridibunda; D051381:Rats; D011919:Rats, Inbred Strains; D012756:Sheep
C495403:Adcyap1 protein, rat; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D000242:Cyclic AMP; D015056:1-Methyl-3-isobutylxanthine