A COMPARATIVE-STUDY OF THE EFFECTS OF DELTA-AMINOLEVULINIC-ACID AND THE GABA(A) AGONIST, MUSCIMOL, IN RAT JEJUNAL PREPARATIONS

Preparations of rat jejunum were tested for their responsiveness to the GABA(A) receptor agonist, muscimol, and to the haem precursor, delta-aminolaevulinic acid (ALA). Both muscimol (1.0-30-mu-M) and ALA (1.0-mu-M-3.0 mM) elicited a concentration-dependent increase in tone. Pretreatment with the GABA(A) antagonist, bicuculline (10(-5) M), blocked effects of muscimol at all concentrations tested and attenuated effects of 0.3 mM ALA. However, bicuculline enhanced responsiveness of the preparations to ALA at low concentrations (0.01-0.05-mu-M), as also did picrotoxin (10(-5) M), eliciting a significant increase of tone. The significance of these findings is discussed. This finding of pharmacological activity by ALA at concentrations comparable with its blood levels during acute attacks of intermittent porphyria provides support for the proposal that is may play a role in the aetiology of the gastrointestinal manifestations of this disease.