Alpha-2 adrenoceptor in rat jejunum epithelial cells: characterization with [3H]RX821002 and distribution along the villus-crypt axis.
Alpha-2 adrenergic receptivity of rat jejunum epithelial cells was studied using the new antagonist radioligand, [3H]RX821002 [( 3H]-2-(2-methoxy-1,4-benzodioxan-2-yl)-2-imidazoline). All the parameters of [3H]RX821002 binding were consistent with the labeling of an alpha-2 adrenoceptor. The use of this probe was moreover extremely convenient, because contrarily to [3H]yohimbine and [3H]rauwolscine, [3H]RX821002 displayed in this tissue a very high affinity (Kd = 0.54 +/- 0.12 nM) and a low level of nonspecific binding (5% at 1 nM [3H]RX821002). Competition studies with various antagonists and agonists showed that the labeled sites were alpha-2-selective and stereospecific. Oxymetazoline was much more potent than chlorpromazine or prazosin suggesting that the receptor is of the alpha-2-subtype. Yohimbine and rauwolscine were equipotent, which is also in agreement with the pharmacological definition of this subtype. These two compounds displayed, however, a rather weak affinity (Ki approximately 40 nM), which is somewhat different with what one should expect for a true alpha-2A adrenoceptor. Altogether the competition data indicated that the alpha-2 adrenoceptor from rat jejunal epithelium is neither an alpha-2A, nor an alpha-2B, nor an alpha-2c adrenoceptor and may belong to a fourth subtype.(ABSTRACT TRUNCATED AT 250 WORDS)
Paris
H
H
Institut National de la Santé et de la Recherche Médicale, Institut de Physiologie, Toulouse, France.
Voisin
T
T
Remaury
A
A
Rouyer-Fessard
C
C
Daviaud
D
D
Langin
D
D
Laburthe
M
M
D000316:Adrenergic alpha-Agonists / Q000378:metabolism* / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive; D004146:Dioxanes / Q000378:metabolism* / Q000494:pharmacology; D004147:Dioxins / Q000378:metabolism*; D004347:Drug Interactions; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D019329:Idazoxan / Q000031:analogs & derivatives; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D004147:Dioxins; D011942:Receptors, Adrenergic, alpha; C058525:2-methoxyidazoxan; D019329:Idazoxan