Parathyroid hormone fragments relax guinea pig trachea in vitro

Synthetic bovine parathyroid hormone (PTH) fragment containing the N-terminal 1-34 amino acids, Bpth-(1-34), relaxed the guinea pig trachea constricted with histamine in vitro. Peptides with bovine and human sequences produced similar effects. Substitution of methionine at positions 8 and 18 by norleucine did not affect this property of Bpth-(1-34). However, after the methionines were oxidized by treating the peptide with hydrogen peroxide, the peptide no longer produced a relaxation in the trachea. Oxidation of the methionine-replaced analog did not affect the action of the peptide on the trachea. It seems that the methionines per se are dispensable, but once oxidized the conformation of the molecule is sufficiently altered to affect its ability to relax the trachea. Propranolol which blocks the relaxing action of isoproterenol did not inhibit the Bpth-(1-34) effect. This action of PTH on the trachea may be related to cAMP since iso-butyryl-methyl-xanthine (a phosphodiesterase inhibitor) potentiates and imidazole (a phosphodiesterase stimulator) inhibits the trachea relaxing action of bPTH-(1-34).