ISSN:
1432-1912
Schlagwort(e):
[D-Trp7]Sendide
;
NK1 antagonist
;
Intrathecal injection
;
Scratching, biting and licking
;
NK1 receptor binding
Quelle:
Springer Online Journal Archives 1860-2000
Thema:
Medizin
Notizen:
Abstract An analogue of sendide, [DTrp7]sendide, was newly synthetized and evaluated as a putative NK1 receptor antagonist in a mouse behavioural test. Effects of [DTrp7]sendide on the scratching, biting and licking response induced by substance P (SP), neurokinin A (NK A) and neurokinin B (NK B) was studied after intrathecal injections. When administered simultaneously with SP, an endogenous agonist for NK1 receptors, [DTrp7]sendide inhibited the behavioural response to this tachykinin in a dose-dependent manner with ID50 value of 1 t.0 pmol/mouse. The behavioural response elicited by other NK1 receptor agonists, septide and physalaemin, was reduced significantly by a small dose (32.0 pmol) of [DTrp7]sendide. Large doses (nmol order) of [DTrp7]sendide were needed to reduce the characteristic behaviour of NK A, an NK2 agonist, NK B, an NK3 agonist and eledoisin, an NK2/NK3 agonist. The duration of the antagonistic effect of [DTrp7]sendide was relatively longer. In a [3H]labeled SP binding assay using mouse spinal cord membranes, [DTrp7]sendide potently displaced [3H] labeled SP binding with a Ki value of 0.023 ± 0.007 nM, which was approximately 140 and 9400 times more potent than that of unlabeled SP and CP-96,345, respectively. These findings suggest that [DTrp7]sendide interacts selectively with the NK1 receptor in the mouse spinal cord as assayed by the receptor binding and SP-induced behavioural tests.
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1007/BF00178956
Permalink
