Premium
Pharmacological analysis of [ 3 H]‐senktide binding to NK 3 tachykinin receptors in guinea‐pig ileum longitudinal muscle‐myenteric plexus and cerebral cortex membranes
Author(s) -
Guard Steven,
Watson Stephen P.,
Maggio John E.,
Too H. Phon,
Watling Keith J.
Publication year - 1990
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1990.tb13004.x
Subject(s) - substance p , neurokinin a , myenteric plexus , neurokinin b , tachykinin receptor , medicine , endocrinology , eledoisin , biology , agonist , ileum , receptor , neuropeptide , biochemistry , immunohistochemistry
1 The binding properties and pharmacological specificity of the selective NK 3 tachykinin receptor agonist [ 3 H]‐senktide ([ 3 H]‐succinyl[Asp 6 ,MePhe 8 ] substance P (6–11)) have been examined in homogenates of guinea‐pig ileum longitudinal muscle‐myenteric plexus (LM/MP) and cerebral cortex. 2 Scatchard analysis of saturation binding studies in guinea‐pig ileum LM/MP and cerebral cortex membranes indicated that [ 3 H]‐senktide bound to a single site with apparent high affinity, K D = 2.21 ± 0.65 n m ; B max = 13.49 ± 0.04 fmol mg −1 protein in ileum and K D = 8.52 ± 0.45 n m ; B max = 76.3 ± 1.6 fmol mg −1 protein in cortex (values are means ± ranges; n = 2). 3 The pharmacological profile for tachykinins and analogues in displacing [ 3 H]‐senktide from ileum membranes was: [MePhe 7 ] neurokinin B > neurokinin B (NKB) ≃ senktide > eledoisin > substance P (SP) > neurokinin A(NKA) > physalaemin > [Sar 9 ,Met(O 2 ) 11 ]SP > [Nle 10 ]NKA(4–10) = [Glp 6 ,L‐Pro 9 ]‐SP(6–11) > substance P methyl ester, consistent with [ 3 H]‐senktide binding to an NK 3 subtype of tachykinin receptor. A similar rank order of affinity was obtained for these peptides in displacing [ 3 H]‐senktide from cortex membranes 4 Several tachykinin receptor agonists were tested for their ability to displace [ 3 H]‐senktide from ileal and cortical NK 3 binding sites and were found to be either weak displacers (pIC 50 < 5.00) or inactive. 5 The binding of [ 3 H]‐senktide to cortex membranes was inhibited by GTP (pIC 50 = 6.49)and GTP‐γ‐S (pIC 50 = 6.67) with ATP being at least three orders of magnitude less potent (pIC 50 = 3.55). 6 These results indicate that both central and peripheral NK 3 receptors share a similar pharmacological specificity and that they may be labelled selectively with the NK 3 receptor agonist [ 3 H]‐senktide.