Novel selective agonists and antagonists confirm neurokinin NK 1 receptors in guinea‐pig vas deferens

1 The aim of this study was the pharmacological characterization of tachykinin NKI and NK2 receptors mediating contraction in the circular muscle of the guinea-pig ileum and proximal colon. The action of substance P (SP), neurokinin A (NKA) and of the synthetic agonists [ Furthermore, an intraspecies heterogeneity of the NK2 receptor in the circular muscle of the guinea-pig ileum and colon is suggested.

Section: Discussioncontrasting

confidence: 46%

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

Maggi

Patacchini

Meini

et al. 1994

“…Previous studies have implicated TKs as transmitters in the atropine-resistant contraction of the circular muscle of the guinea-pig ileum produced by electrical field stimulation or stimulation of the ascending enteric reflex (Costa et al, 1985a,b;Holzer, 1989 receptor activation with a pA2 value of 7.7-7.8 (Hagan et al, 1990;Hall & Morton, 1991 (Holzer, 1989) and may indicate a partial involvement of TKs in the ascending enteric reflex evoked in the absence of atropine. Confirming .K, and NK2 tachy-previous observations (Holzer, 1989) larger volumes of balscle contraction proloon distension were required to evoke maximal noncholinernerves in the ileum.…”

Section: Discussionmentioning

confidence: 99%

“…All experiments started after a 120 min equilibration period. In a first series of experiments, three different receptorselective tachykinin antagonists, GR 71251 (NK1 receptor selective, Hagan et al, 1990;Hall & Morton, 1991) In a second series of experiments, the selectivity of antagonists was tested against circular muscle contractions produced by the NK1 receptor-selective agonist [Sari substance P sulphone (Drapeau et al, 1987) …”

Section: Circular Muscle Stripsmentioning

confidence: 99%

Tachykininergic transmission to the circular muscle of the guinea‐pig ileum: evidence for the involvement of NK₂ receptors

Barthó

Santicioli

Patacchini

et al. 1992

1 The effect of newly developed, receptor-selective tachykinin antagonists (GR 71,251 for NK1 receptors, MEN 10,376 and L 659,877 for NK2 receptors) on noncholinergic transmission to the circular muscle of the guinea-pig ileum has been investigated. 2 In circular muscle strips of the ileum, electrical field stimulation in the presence of atropine (2 jM) and apamin (0.1 jAM) evoked a complex motor response. The tonic primary contraction in this response was reduced by GR 71,251 (10 jM) and MEN 10,376 (3-10 I1M) but not by L 659,877 (up to 10 jM). The presence of apamin was necessary in this experimental arrangement to unmask an atropine-resistant primary contraction, sensitive to tachykinin antagonists. The motor response was abolished by tetrodotoxin.3 In circular strips of the ileum GR 71,251 (10 jM) inhibited the tonic contraction produced by [Sar9] substance P sulphone, a selective NK1 receptor agonist but not that produced by [,B Alal] neurokinin A (4-10), a selective NK2 receptor agonist. By contrast, MEN 10,376 antagonized the effect of the NK2 agonist while leaving the response to the NK, agonist unaffected. 4 In whole segments of the ileum, distension of the gut wall by an intraluminal balloon placed at about 1 cm from the point of recording of mechanical activity of the circular muscle produced atropinesensitive phasic contractions (ascending enteric reflex). In the presence of atropine (2 jiM), a noncholinergic response was elicited, which required larger volumes of distension that the cholinergic one. The atropine-resistant ascending enteric reflex was enhanced by apamin (0.1 j1M) and abolished by tetrodotoxin, either in the presence or absence of apamin. 5 MEN 10,376 (3-lOM) inhibited the atropine-resistant ascending enteric reflex in the presence of apamin while GR 71,251 or L 659,877 (10 lM each) were ineffective. MEN 10,376 inhibited the atropine-resistant ascending enteric reflex to a larger extent in the absence than in the presence of apamin and also slightly inhibited the ascending enteric reflex in the absence of atropine. 6 These findings provide evidence for an involvement of NK2 tachykinin receptors in excitatory transmission to the circular muscle of the guinea-pig ileum. NK2 receptors are also involved in the physiological-like circular muscle activation produced by stimulation of intramural neuronal pathways which subserve the atropine-resistant ascending enteric reflex.

“…Indeed, the converse tended to occur. Tachykinin receptor antagonists have been found to exhibit agonistdependence in other tissue preparations which seem to contain only one type of tachykinin receptor (see Bailey, 1985;Bailey et al, 1986;Hall & Morton, 1991) but definitive explanation of such behaviour is awaited. In the rabbit trachea, both L-659,877 and R396 had effects qualitatively and quantitatively similar to those in guinea-pig trachea.…”

Section: Discussionmentioning

confidence: 99%

Receptors mediating tachykinin‐induced contractile responses in guinea‐pig trachea

Ireland

Bailey

Cook

et al. 1991

1 The classification of tachykinin receptors in the guinea-pig trachea has been investigated. This 5 For L-659,877 and R396, comparison was made between activity in guinea-pig trachea and in preparations known to contain tachykinin receptors predominantly of the NK2 type. In the rabbit trachea, both L-659,877 and R396 had effects similar to those in guinea-pig trachea. In contrast, in the rat colon muscularis mucosae, both L-659,877 and R396 appeared to behave competitively with pKB values against GR64349 of 7.83 and 6.90 respectively. 6 It is concluded that in guinea-pig trachea, contractile responses can be induced by activation of both NK1 and NK2 receptors. The present data are discussed with reference to the proposed existence of subtypes of the NK2 receptor.