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Anti-peptide antibodies sensitive to the 'active' state of the beta2-adrenergic receptor
A Mijares1, D Lebesgue, J Argibay
1CNRS UMR 6542, Physiologie des Cellules Cardiaques et Vasculaires, Faculté des Sciences, UFR Sciences Pharmaceutiques, Tours, France.
Antibodies directed against a peptide corresponding to the second loop of the human beta2-adrenergic receptor were induced in rabbits by immunisation with the free peptide in complete Freund's adjuvant. The resulting antibodies were affinity-purified and shown to be monospecific for the target receptor. They were able to stimulate the L-type Ca2+ channels in whole-cell patch-clamp experiments on isolated adult guinea-pig cardiomyocytes. This effect was similar to that obtained by the specific beta2-adrenergic agonist zinterol. The antibody effects could be blocked with the specific beta2-adrenergic inverse agonist ICI118,551 but not with the neutral antagonist alprenolol. These results suggest that the antibodies recognise the active conformer of the beta2-adrenergic receptor.
Antibodies directed against a peptide corresponding to the second loop of the human beta2-adrenergic receptor were induced in rabbits by immunisation with the free peptide in complete Freund's adjuvant. The resulting antibodies were affinity-purified and shown to be monospecific for the target receptor. They were able to stimulate the L-type Ca2+ channels in whole-cell patch-clamp experiments on isolated adult guinea-pig cardiomyocytes. This effect was similar to that obtained by the specific beta2-adrenergic agonist zinterol. The antibody effects could be blocked with the specific beta2-adrenergic inverse agonist ICI118,551 but not with the neutral antagonist alprenolol. These results suggest that the antibodies recognise the active conformer of the beta2-adrenergic receptor.