A pharmacological comparison of [3H]-granisetron binding sites in brain and peripheral tissues of the mouse.
The affinities of a range of structurally diverse 5-HT3 receptor agonists and antagonists for [3H]-granisetron binding sites have been measured in membrane homogenates prepared from central and peripheral tissues of the mouse. By comparing the affinities of compounds across these tissues, the question of whether intra-species 5-HT3 receptor subtypes exist in the mouse has been addressed. In entorhinal cortex and brainstem, [3H]-granisetron bound to a single high affinity saturable binding site (Kd 0.47 +/- 0.14 and 0.60 +/- 0.05 nM; Bmax 20 +/- 6 and 7 +/- 2 fmol (mg protein)-1 respectively; mean +/- SEM; n = 3). In distal and proximal colon, the specific binding of [3H]-granisetron was best fitted to a 2-site model. Kd values obtained for the high affinity site were similar to those obtained in brain tissue (distal colon: 0.47 +/- 0.09 nM, n = 4; proximal colon: 0.39 +/- 0.09 nM, n = 4). In salivary gland, 2-sites were evident in 2 out of 4 experiments. The Kd value (calculated from the high affinity site in the 2-site model) was approximately 10-fold less than in brain or colon (3.3 +/- 1.1 nM, n = 4). Bmax values were 7 +/- 2, 4 +/- 1 and 71 +/- 16 fmol (mg protein)-1 for distal colon, proximal colon and salivary gland respectively. For all tissues the estimated affinity of the low affinity site was variable, and Bmax values could not be reliably calculated.(ABSTRACT TRUNCATED AT 250 WORDS)
Perren
M J
MJ
Department of Pharmacology, Glaxo Group Research Ltd, Ware, Hertfordshire, UK.
Rogers
H
H
Mason
G S
GS
Bull
D R
DR
Kilpatrick
G J
GJ
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D001921:Brain / Q000378:metabolism*; D003106:Colon / Q000187:drug effects / Q000378:metabolism; D017829:Granisetron / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008566:Membranes / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D011869:Radioligand Assay; D011985:Receptors, Serotonin / Q000187:drug effects*; D012469:Salivary Glands / Q000187:drug effects / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D017829:Granisetron; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists