European Journal of Pharmacology, 145 (1988) 335-340 335 Elsevier EJP 50093 Contractile response of the human isolated urinary bladder to neurokinins: involvement of NK-2 receptors Carlo Alberto Maggi *, Paolo Santicioli, Riccardo Patacchini, Martino Cellerini, Damiano Turini 1, Gabriele Barbanti 1, Patrizia Beneforti 1, Paolo Rovero z and Alberto Meli Pharmacology Department, Smooth Muscle Division, Res. Labs., A. Menarini Pharmaceuticals, Via Sette Santi 3, Florence 50131, 1 Department of Urology, University ofFerrara, 2 Chemistry Department, A. Menarini Pharmaceuticals, Florence, Italy Received27 July 1987, revised MS received7 October 1987, accepted 27 October 1987 The contractile response to substance P (SP), neurokinin A (NKA) and arginin-neurokinin B (Arg-NKB) (a water soluble analogue of NKB) was investigated in detrusor muscle strips from the dome of the urinary bladder obtained from patients undergoing total cystectomy for carcinoma of the bladder base. Spontaneous activity and response to nerve stimulation indicated that the material used in this study has characteristics similar to those described for 'normal' human detrusor muscle. All neurokinins induced a concentration-related contraction with sensitivity at nM concentrations and the following rank order of potency: NKA (90) > Arg-NKB (22) > SP (1). These findings indicate the involvement of NK-2 receptors in the contractile response of human detrusor muscle to neurokinins. Neurokinins; Urinary bladder; Neurokinin receptors; (Human) 1. Introduction In recent years, it has been shown that multiple receptors mediate the functional response to tachykinins (e.g. neurokinins) in various mam- malian tissues (Lee et al., 1982). Both radioligand and functional assays indicate the existence of three' receptors' which can be identified by specific patterns in the rank order of potency of agonists (Regoli et al., 1985; 1986; 1987; Buck et al., 1984; Lee et al., 1986; Maggi et al., 1987b). Neurokinins have potent biological effects on smooth muscles from the mammalian urinary tract and their pe- ripheral release may have important pathophysio- logical consequences for the regulation of vesi- courethral motility (Maggi and Meli, 1986; in press). Substance P has been reported to induce a contraction of the human detrusor muscle but this * To whom all correspondence should be addressed. effect appeared only at quite high concentrations (Erspamer et al., 1981; Kalbfleisch and Daniel, 1987). On the other hand, the non-mammalian tachykinins, eledoisin and kassinin were reported to be at least 50 times more potent than SP in contracting the human isolated bladder (Erspamer et al., 1981). The recent discovery of the new Kassinin-like neurokinins (neurokinin A, NKA, neurokinin B, NKB) (see Maggio, 1985 for review), prompted studies on their pharmacological prop- erties. NKA and NKB produced potent motor effects in the rat lower urinary tract which could involve activation of NK-A or NK-B receptors (Maggi et al., 1987a,c), sites for which SP has a low affinity (Regoli et al., 1986; 1987; Lee et al., 1986; Burcher and Buck, 1986). According to the new nomenclature for tachykinin receptors (adopted at a general meeting during the Sub- stance P and Neurokinins Symposium, Montreal July 1986) NK-A and NK-B receptors have been renamed NK-2 and NK-3, respectively. We now 0014-2999/88/$03.50 © 1988 ElsevierSciencePubhshers B.V. (BiomedicalDivision)