Abstract
RO 25-1553 is a synthetic VIP analogue that induced a long-lasting relaxation of tracheal and bronchial smooth muscles as well as a reduction of edema and eosinophilic mobilization during pulmonary anaphylaxis. In the present study, we tested in vitro the capacity of RO 25-1553 to occupy the different VIP/PACAP receptor subclasses and to stimulate adenylate cyclase activity. The cellular models tested expressed one single receptor subtype: Chinese hamster ovary (CHO) cells transfected with the rat recombinant PACAP I, rat VIP1, and human VIP2 receptors; SUP T1 cells expressing the human VIP2 and HCT 15 and LoVo cells expressing the human VIP1 receptor. RO 25-1553 was threefold more potent than VIP on the human VIP2 receptor, 100- and 600-fold less potent than VIP on the rat and human VIP1 receptors, respectively, and 10-fold less potent than VIP and 3000-fold less potent than PACAP on the PACAP I receptor. RO 25-1553 was a full agonist on the VIP2, the PACAP I, and the rat recombinant VIP1 receptor but a partial agonist only on the human VIP1 receptor. Thus, RO 25-1553 is a highly selective agonist ligand for the VIP2 receptor subclass.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenylyl Cyclases / metabolism
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Amino Acid Sequence
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Animals
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CHO Cells
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Cricetinae
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Enzyme Activation / drug effects
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Humans
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Molecular Sequence Data
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Neuropeptides / chemical synthesis
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Neuropeptides / pharmacology
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Peptides, Cyclic / agonists
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Peptides, Cyclic / pharmacology*
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Pituitary Adenylate Cyclase-Activating Polypeptide
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Rats
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Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide
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Receptors, Pituitary Hormone / drug effects
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Receptors, Vasoactive Intestinal Peptide / chemistry
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Receptors, Vasoactive Intestinal Peptide / drug effects*
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Receptors, Vasoactive Intestinal Peptide / metabolism*
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Receptors, Vasoactive Intestinal Peptide, Type II
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Receptors, Vasoactive Intestinal Polypeptide, Type I
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Recombinant Proteins
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Transfection
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Tumor Cells, Cultured
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Vasoactive Intestinal Peptide / agonists
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Vasoactive Intestinal Peptide / analogs & derivatives*
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Vasoactive Intestinal Peptide / pharmacology
Substances
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ADCYAP1 protein, human
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Adcyap1 protein, rat
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Neuropeptides
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Peptides, Cyclic
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Pituitary Adenylate Cyclase-Activating Polypeptide
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Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide
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Receptors, Pituitary Hormone
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Receptors, Vasoactive Intestinal Peptide
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Receptors, Vasoactive Intestinal Peptide, Type II
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Receptors, Vasoactive Intestinal Polypeptide, Type I
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Recombinant Proteins
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Ro 25-1553
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Vasoactive Intestinal Peptide
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Adenylyl Cyclases