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Research Article Free access | 10.1172/JCI116427

Characterization and distribution of alpha 2-adrenergic receptors in the human intestinal mucosa.

P Valet, J M Senard, J C Devedjian, V Planat, R Salomon, T Voisin, G Drean, A Couvineau, D Daviaud, and C Denis

Institut National de la Santé et de la Recherche Médicale, (INSERM) U317, Institut Louis Bugnard, Centre Hospitalier Universitaire Rangueil, Toulouse, France.

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Institut National de la Santé et de la Recherche Médicale, (INSERM) U317, Institut Louis Bugnard, Centre Hospitalier Universitaire Rangueil, Toulouse, France.

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Institut National de la Santé et de la Recherche Médicale, (INSERM) U317, Institut Louis Bugnard, Centre Hospitalier Universitaire Rangueil, Toulouse, France.

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Institut National de la Santé et de la Recherche Médicale, (INSERM) U317, Institut Louis Bugnard, Centre Hospitalier Universitaire Rangueil, Toulouse, France.

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Institut National de la Santé et de la Recherche Médicale, (INSERM) U317, Institut Louis Bugnard, Centre Hospitalier Universitaire Rangueil, Toulouse, France.

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Institut National de la Santé et de la Recherche Médicale, (INSERM) U317, Institut Louis Bugnard, Centre Hospitalier Universitaire Rangueil, Toulouse, France.

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Institut National de la Santé et de la Recherche Médicale, (INSERM) U317, Institut Louis Bugnard, Centre Hospitalier Universitaire Rangueil, Toulouse, France.

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Institut National de la Santé et de la Recherche Médicale, (INSERM) U317, Institut Louis Bugnard, Centre Hospitalier Universitaire Rangueil, Toulouse, France.

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Institut National de la Santé et de la Recherche Médicale, (INSERM) U317, Institut Louis Bugnard, Centre Hospitalier Universitaire Rangueil, Toulouse, France.

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Institut National de la Santé et de la Recherche Médicale, (INSERM) U317, Institut Louis Bugnard, Centre Hospitalier Universitaire Rangueil, Toulouse, France.

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Published May 1, 1993 - More info

Published in Volume 91, Issue 5 on May 1, 1993
J Clin Invest. 1993;91(5):2049–2057. https://doi.org/10.1172/JCI116427.
© 1993 The American Society for Clinical Investigation
Published May 1, 1993 - Version history
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Abstract

The subtype and the expression of the alpha 2-adrenergic receptor were investigated in the normal mucosa from human intestine by means of radioligand binding, RNase mapping, and measurement of adenylate cyclase activity. The study of the binding of the alpha 2-adrenergic antagonist, [3H]RX821002, to epithelial cell membranes indicated the existence of a single class of noninteracting sites displaying a high affinity for the radioligand (Kd = 1.1 +/- 0.5 nM). The rank order of potency of antagonists to inhibit [3H]RX821002 binding (RX821002 > yohimbine = rauwolscine > phentolamine approximately idazoxan >> chlorpromazine > prazosin) suggested that the receptor is of the alpha 2A subtype. A conclusion which is confirmed by the fact that only alpha 2C10 transcripts were found in the human intestine mucosa. Competition curves with (-)-norepinephrine demonstrated that 60% of the receptor population exhibited high affinity for agonists. This high-affinity state was abolished by the addition of GTP plus Na+ or by prior treatment of the membranes with pertussis toxin indicating it corresponded to G protein-coupled receptors. [32P]ADP-ribosylation and immunoblotting experiments identified two pertussis toxin-sensitive G proteins corresponding to Gi2 and Gi3. The study of the distribution of the receptor indicated that (a) the proximal colon is the intestine segment exhibiting the highest receptor density and (b) the receptor is predominantly expressed in crypts and is preferentially located in the basolateral membrane of the polarized cell. The distribution of the receptor along the crypt-surface axis of the colon mucosa can be correlated with a higher level of alpha 2C10-specific mRNA and a higher efficiency of UK14304 to inhibit adenylate cyclase in crypt cells.

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