title: Bronchodilating properties of the VIP receptor agonist Ro 25-1553 compared to those of formoterol on the guinea-pig isolated trachea.
abstract: Ro 25-1553 is a 31-amino acid analogue of vasoactive intestinal peptide (VIP) and has recently been shown to be highly selective for the VPAC(2)-receptor. The bronchodilating property of this compound was evaluated in vitro on preparations of guinea-pig trachea, with the long-acting beta(2)-adrenoceptor selective agonist, formoterol, as a reference. In strip-preparations precontracted with carbachol, Ro 25-1553 caused a concentration-dependent and complete relaxation of the tracheal smooth muscle. Ro 25-1553 was 3-7 times less potent than formoterol on a molar basis, but the efficacy was comparable with that of formoterol. Both compounds showed a rapid onset of action and a similar durability of effect. Ro 25-1553 appeared to interact with formoterol as well as with salmeterol in an additive way. In vagus nerve-trachea tube preparations, when added to the external medium, Ro 25-1553 concentration-dependently and completely inhibited nerve-induced contractions. This occurred in the same concentration range as needed for relaxation of precontracted strips. Ro 25-1553 was active also when administered into the tracheal lumen albeit the concentration had to be increased. The present study supports and extends previous results suggesting that Ro 25-1553 may be a powerful alternative to the beta(2)-adrenoceptor agonists which prevail today.
authors.affiliation: Clinical Science, AstraZeneca R&D Lund, SE-221 87, Lund, Sweden.
authors.forename: B L
authors.initials: BL
authors.lastname: Källström
authors.forename: B
authors.initials: B
authors.lastname: Waldeck
mesh_terms: D000420:Albuterol / Q000031:analogs & derivatives* / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D001993:Bronchodilator Agents / Q000494:pharmacology*; D002217:Carbachol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004558:Electric Stimulation; D004983:Ethanolamines / Q000494:pharmacology*; D000068759:Formoterol Fumarate; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D008969:Molecular Sequence Data; D009126:Muscle Relaxation / Q000187:drug effects; D010456:Peptides, Cyclic / Q000494:pharmacology*; D018005:Receptors, Vasoactive Intestinal Peptide / Q000819:agonists*; D000068299:Salmeterol Xinafoate; D014132:Trachea / Q000187:drug effects* / Q000294:innervation / Q000502:physiology; D014630:Vagus Nerve / Q000502:physiology; D014660:Vasoactive Intestinal Peptide / Q000031:analogs & derivatives* / Q000494:pharmacology*
chemical_list: D001993:Bronchodilator Agents; D004983:Ethanolamines; D010456:Peptides, Cyclic; D018005:Receptors, Vasoactive Intestinal Peptide; C089777:Ro 25-1553; D014660:Vasoactive Intestinal Peptide; D000068299:Salmeterol Xinafoate; D002217:Carbachol; D000420:Albuterol; D000068759:Formoterol Fumarate