Thiol group may be involved in the irreversible blockade of presynaptic alpha 2-adrenoreceptors by pyrextramine and benextramine in the isolated guinea pig ileum.

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 Sci

journal_title

Life sciences

authors

Brasili L,Cassinelli A,Angeli P,Melchiorre C

doi

10.1016/0024-3205(86)90407-8

subject

Has Abstract

pub_date

1986-05-05 00:00:00

pages

1633-40

issue

18

eissn

0024-3205

issn

1879-0631

pii

0024-3205(86)90407-8

journal_volume

38

pub_type

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