Peripheral effects of neurokinins: functional evidence for the existence of multiple receptors.

The ability of six neurokinins (substance P, neurokinin A, neurokinin B, physalaemin, eledoisin and kassinin) to induce hypotension, salivary secretion and to activate motility of the duodenum and of the urinary bladder was investigated in urethane-anaesthetized rats. A comparison of the relative potency of these substances in producing a given biological effect yielded results consistent with the hypothesis of the existence of three distinct types of receptor in rat peripheral tissues, namely SP-P, SP-K and SP-E according to the nomenclature proposed by Buck, Burcher, Shults, Lovenberg & O'Donohue (1984), or NK-P, NK-A and NK-B according to that of Regoli, D'Orleans-Juste, Drapeau, Dion & Escher (1985). An NK-P receptor is responsible for the production of the hypotensive effect and for the activation of salivary secretion. An 'NK-P like' receptor subtype may be involved in determining the direct contractile effects on muscle cells of neurokinins in the rat isolated urinary bladder and the 'phasic' contraction of the rat duodenum. An NK-A receptor mediates the 'tonic' contraction of the rat duodenum while an NK-B receptor mediates the activation of the micturition reflex. Evidence is presented that multiple neurokinin receptors are present in the same organ and participate with different modalities to the regulation of smooth muscle function.