Possible existence of a new tachykinin receptor subtype in the guinea pig ileum

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

“…injection of selective NK, tachykinin receptor agonists in freely-moving guinea-pigs caused a significant increase in locomotor hyperactivity. This observation is in agreement with previous studies that reported an enhanced locomotion in the guinea-pig (Brent et al, 1988;Seymour et al, 1991) and in the rat (Jolicoeur et al, 1980;Naranjo & Del Rio, 1984 (Petitet et al, 1992;Geraghty et al, 1993;Maggi et al, 1993b;Pradier et al, 1994) The selective NK2 tachykinin receptor agonist [Lys5, Me-Leu9, Nle1INKA(4-10) did not induce, up to the dose of 20 pg, any behavioural responses in the guinea-pig in our experimental design. The data obtained in this species appeared quite different from those reported at the same doses in mice and rats, in which excessive grooming and washing are seen when given various NK2 receptor agonists [Lys5, MeLeu9, Nle'INKA(4-10), NKA and D-septide (Elliott & Iversen, 1986;Sakurada et al, 1989;Tschope et al, 1992;Culman et al, 1993;Picard et al, 1994;Ravard et al, 1994).…”

Comparison of tachykinin NK1 and NK2 receptors in the circular muscle of the guinea‐pig ileum and proximal colon

“…Since pharmacological evidence has been presented to indicate intraspecies heterogeneity of NKI and NK2 receptors (see Introduction), a major aim of the study was to unravel possible differences in receptor antagonist potencies in preparations from the same species. Tachykinin NK3 receptors are also present in the circular muscle of the ileum and their stimulation produces an indirect contractile response (Maggi et al, 1990a (Lee et al, 1986;Wormser et al, 1986;Dion et al, 1987;Laufer et al,-1988;Rovero et al, 1989 [PAla8]NKA(4-10) (c) (Petitet et al, 1992;Meini et al, 1994;Maggi et al, 1993a,b,c;and present (Maggi et at., 1991b Assuming that a 'septide-sensitive' NK1 receptor exists, the rank order of potency of natural tachykinins at this receptor is an obvious question of physiological relevance. Our previous observations (Meini et al, 1994) (Petitet et al, 1992).…”

“…Tachykinin NK3 receptors are also present in the circular muscle of the ileum and their stimulation produces an indirect contractile response (Maggi et al, 1990a (Lee et al, 1986;Wormser et al, 1986;Dion et al, 1987;Laufer et al,-1988;Rovero et al, 1989 [PAla8]NKA(4-10) (c) (Petitet et al, 1992;Meini et al, 1994;Maggi et al, 1993a,b,c;and present (Maggi et at., 1991b Assuming that a 'septide-sensitive' NK1 receptor exists, the rank order of potency of natural tachykinins at this receptor is an obvious question of physiological relevance. Our previous observations (Meini et al, 1994) (Petitet et al, 1992). Since the recognition epitopes for certain NK, receptor antagonists by the NK, receptor protein appear to be distinct from the agonist binding site(s) (Gether et al, 1993) (Fong et al, 1992a (Fong et at., 1992a see also Hermans et at., 1993), in sharp contrast with the high potency of this hexapeptide in various bioassays (e.g.…”

“…For example, septide or [Glp6,ProjSP(6-1 1), a synthetic ligand originally developed as a selective NK1 receptor agonist, displays a contractile activity in the guinea-pig ileum which cannot easily be explained by an interaction with the 'classical' NK1 receptor (Petitet et al, 1992). Petitet et al (1992) proposed that a novel, 'septide-sensitive', tachykinin receptor exists in the guinea-pig ileum.…”

“…For example, septide or [Glp6,ProjSP(6-1 1), a synthetic ligand originally developed as a selective NK1 receptor agonist, displays a contractile activity in the guinea-pig ileum which cannot easily be explained by an interaction with the 'classical' NK1 receptor (Petitet et al, 1992). Petitet et al (1992) proposed that a novel, 'septide-sensitive', tachykinin receptor exists in the guinea-pig ileum. A 'septide-sensitive' receptor was also detected in the rat urinary bladder, which is recognized by NK, receptor antagonists with higher affinity than that observed toward a 'classical' NK, receptor agonist like [Sar9]SP sulphone (Meini et al, 1994).…”