Article date: December 2000
By: Karen P Kerr, Binh Thai, Ian M Coupar in Volume 131, Issue 7, pages 1461-1467
The tachykinin receptor present in the guinea‐pig oesophageal mucosa that mediates contractile responses of the muscularis mucosae has been characterized, using functional in vitro experiments.
The NK1 receptor‐selective agonist, [Sar9(O2)Met11]SP and the NK3 receptor‐selective agonists, [MePhe7]‐NKB and senktide, produced no response at submicromolar concentrations. The NK2 receptor‐selective agonists, [Nle10]‐NKA(4–10), and GR 64,349 produced concentration‐dependent contractile effects with pD2 values of 8.20±0.16 and 8.30±0.15, respectively.
The concentration‐response curve to the non‐selective agonist, NKA (pD2=8.13±0.04) was shifted significantly rightwards only by the NK2 receptor‐selective antagonist, GR 159,897 and was unaffected by the NK1 receptor‐selective antagonist, SR 140,333 and the NK3 receptor‐selective antagonist, SB 222,200.
The NK2 receptor‐selective antagonist, GR 159,897, exhibited an apparent competitive antagonism against the NK2 receptor‐selective agonist, GR 64,349 (apparent pKB value=9.29±0.16) and against the non‐selective agonist, NKA (apparent pKB value=8.71±0.19).
The NK2 receptor‐selective antagonist, SR 48,968 exhibited a non‐competitive antagonism against the NK2 receptor‐selective agonist, [Nle10]‐NKA(4–10). The pKB value was 10.84±0.19.
It is concluded that the guinea‐pig isolated oesophageal mucosa is a useful preparation for studying the effects of NK2 receptor‐selective agonists and antagonists as the contractile responses to various tachykinins are mediated solely by NK2 receptors.
The tachykinin receptor present in the guinea‐pig oesophageal mucosa that mediates contractile responses of the muscularis mucosae has been characterized, using functional in vitro experiments.
The NK1 receptor‐selective agonist, [Sar9(O2)Met11]SP and the NK3 receptor‐selective agonists, [MePhe7]‐NKB and senktide, produced no response at submicromolar concentrations. The NK2 receptor‐selective agonists, [Nle10]‐NKA(4–10), and GR 64,349 produced concentration‐dependent contractile effects with pD2 values of 8.20±0.16 and 8.30±0.15, respectively.
The concentration‐response curve to the non‐selective agonist, NKA (pD2=8.13±0.04) was shifted significantly rightwards only by the NK2 receptor‐selective antagonist, GR 159,897 and was unaffected by the NK1 receptor‐selective antagonist, SR 140,333 and the NK3 receptor‐selective antagonist, SB 222,200.
The NK2 receptor‐selective antagonist, GR 159,897, exhibited an apparent competitive antagonism against the NK2 receptor‐selective agonist, GR 64,349 (apparent pKB value=9.29±0.16) and against the non‐selective agonist, NKA (apparent pKB value=8.71±0.19).
The NK2 receptor‐selective antagonist, SR 48,968 exhibited a non‐competitive antagonism against the NK2 receptor‐selective agonist, [Nle10]‐NKA(4–10). The pKB value was 10.84±0.19.
It is concluded that the guinea‐pig isolated oesophageal mucosa is a useful preparation for studying the effects of NK2 receptor‐selective agonists and antagonists as the contractile responses to various tachykinins are mediated solely by NK2 receptors.
British Journal of Pharmacology (2000) 131, 1461–1467; doi:10.1038/sj.bjp.0703708
DOI: 10.1038/sj.bjp.0703708
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