Receptor subtypes or species homologues: relevance to drug discovery

Comparative behavioural profile of centrally administered tachykinin NK1, NK2 and NK3 receptor agonists in the guinea‐pig

“…A pharmacological heterogeneity of this receptor has been also demonstrated: the NK2 tachykinin receptor expressed in guinea-pig, rabbit and human smooth muscle is distinct from that expressed in rat or hamster smooth muscle (Maggi et al, 1991;. Thus the apparent discrepancy between our results and those previously reported in rodents may be species-related (Hall et al, 1993). Even if Stratton et al (1993) have observed anxiolytic-like properties of different tachykinin NK2 receptor antagonists in the mouse light/dark box test, and despite some evidence suggesting the presence of discrete NK2 tachykinin binding sites in the mammalian brain (Dam et al, 1990), the involvement of NK2 tachykinin receptors in centrally-related behaviours still remains to be confirmed.…”

Bradykinin B1 receptors in the rabbit urinary bladder: induction of responses, smooth muscle contraction, and phosphatidylinositol hydrolysis

“…The B1 receptorselective antagonist, [Leu8,des-Argl-BK had a similar affinity in both preparations (pKB estimates of 6.1 and 6.3, respectively). The affinity of [Leu8,des-Arg']-BK in these two preparations is lower than its affinity reported previously in the rabbit aorta (pA2 6.8; Regoli et al, 1978) and mesenteric artery (pA2 6.5; Churchill & Ward, 1986 (Regoli & Barab6, 1980;Butt et al, 1994a,b), and no complication in interpretation due to differences between species needs to be taken into account (see Hall, 1992;Hall et al, 1993). The novel B1 receptor antagonist [des-Arg'I-Hoel40 (Wirth et al, 1991) has a ten fold higher affinity than [Leu8,des-Argl-BK.…”

Inhibition of bradykinin‐evoked trigeminal nerve stimulation by the non‐peptide bradykinin B2 receptor antagonist WIN 64338 in vivo and in vitro

“…A number of 'first-generation' peptide bradykinin antagonists also showed differences in affinity for B2 receptors in different isolated preparations . Thus these various data suggest that WIN 64388, as with peptide antagonists, can distinguish between species homologues or receptor subtypes of bradykinin B2 receptors (see Hall et al, 1993a).…”