TACHYKININ-INDUCED CONTRACTIONS OF THE GUINEA-PIG ILEUM LONGITUDINAL SMOOTH-MUSCLE - TONIC AND PHASIC MUSCULAR ACTIVITIES

In vitro tachykinin-induced contractions of guinea pig ileum longitudi nal smooth muscle were investigated under isometric conditions by usin g selective agonists ([Sar(9),Met(O-2)(11)]substance P, [Nle(10)]neuro kinin A-(4-10), senktide) and antagonists (SR 140333, SR 48968, SR 142 801), respectively for the tachykinin NK1, NK2, and NK3 receptors. [Sa r(9),Met(O-2)(11)]Substance P (10 nM) induced a tonic contraction with superimposed phasic contractions. Both tonic and phasic muscular acti vities were completely abolished by SR 140333 (10 nM) and were not mod ified by SR 142801 (10 nM). SR 48968 (10 nM) and atropine (0.001 mM) d id not modify the tonic muscular activity but inhibited the phasic mus cular activity. [Nle(10)]Neurokinin A-(4-10) (10 nM) only caused a pha sic contractile response that was inhibited by SR 48968. Atropine, SR 140333, and SR 142801 were without effect. Senktide (1 nM) induced com bined tonic and phasic contractile responses. SR 142801 blocked the ph asic and tonic muscular activities, whereas SR 48968 and SR 140333 wer e inactive. After addition of atropine, only tonic contractile respons e was abolished. These results showed fundamental differences in isome tric tonic and phasic contractile responses of guinea pig ileum longit udinal smooth muscle to tachykinins.