Conformational requirements of alpha 2-adrenergic receptors.
The conformationally restrained trans-extended and cis-folded isomers of 2-(3,4-dihydroxyphenyl)cyclobutylamine were used to establish the conformational requirements of presynaptic alpha 2-adrenergic receptors in the field-stimulated guinea pig ileum. The trans-extended isomer produced a concentration-dependent inhibition of the twitch response with an EC50 of 34 microM. The cis-folded analogue failed to produce a significant inhibition of the twitch response at concentrations up to 1 mM. These results suggest that the presynaptic alpha 2-adrenergic receptor prefers phenethylamines in the trans-extended conformation over the cis-folded conformation. The conformational requirements of alpha 1- and alpha 2-adrenergic receptors appear to be similar.
D000818:Animals; D004298:Dopamine / Q000494:pharmacology; D004558:Electric Stimulation; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008968:Molecular Conformation; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000187:drug effects; D009638:Norepinephrine / Q000031:analogs & derivatives / Q000494:pharmacology; D011941:Receptors, Adrenergic / Q000378:metabolism*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism*; D013237:Stereoisomerism; D013469:Sulpiride / Q000494:pharmacology
D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D013469:Sulpiride; D004298:Dopamine; D009638:Norepinephrine