ABSTRACT
The cross influence of polypeptides (substance P, eledoisin) and neurotransmitters (acetylcholine, histamine, 5-hydroxytryptamine, ATP) on isolated guinea pig ileum involved a reduction or loss of muscle sensitivity. After the desensitization induced by one of the neurotransmitters the sensitivity of the ileum longitudinal muscle to polypeptides as estimated by the dissociation constant of the drug-receptor complex, decreased, i.e. a non-specific cross desensitization occurred. 5-hydroxytrpyptamine, however, increased the sensitivity to the polypeptides. A similar sensibilizing effect is characteristic of the polypeptides which, after application, increased 1.5-2.0-fold the height of the maximum muscle contraction and decreased 2-4-fold the dissociation constant. A possible involvement of polypeptides not only in their interaction with the target cells but also in the modulation of neurotransmitters, is discussed.