Abstract:
:This study, conducted on isolated guinea pig ileum, was designed to establish the mechanism of presynaptic alpha 2-adrenoreceptor blockade by the tetramine disulfides, benextramine and pyrextramine. At 1 microM these drugs irreversibly blocked norepinephrine (NE)-induced inhibition of the twitch response to electrical stimulation. This may be the result of covalent bond formation between the disulfide bridge of the inhibitor and a thiol function at the receptor level through an interchange reaction since the benextramine carbon analogue did not affect NE response under the same conditions. Furthermore, NE (10 microM) failed to protect presynaptic alpha 2-adrenoreceptors from pyrextramine blockade whereas idazoxan (O.T microM) completely abolished the irreversible antagonism of pyrextramine (1 microM). This finding suggests that the tetramine disulfide binding site may coincide with that of idazoxan and is different from the NE binding site.
journal_name
Life Scijournal_title
Life sciencesauthors
Brasili L,Cassinelli A,Angeli P,Melchiorre Cdoi
10.1016/0024-3205(86)90407-8subject
Has Abstractpub_date
1986-05-05 00:00:00pages
1633-40issue
18eissn
0024-3205issn
1879-0631pii
0024-3205(86)90407-8journal_volume
38pub_type
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