1. Brief exposure for 2 min of guinea-pig isolated ileum to [Met5]
enkephalin (MEnk) and
noradrenaline has been shown previously to produce withdrawal
contractures on washout of the agonist or addition of
naloxone (MEnk) or
phentolamine (
noradrenaline). 2. The present study was undertaken to investigate firstly, whether other putative
neurotransmitters and/or related drugs which inhibit transmitter release also produced withdrawal responses following 2 min contact with the ileum and secondly, whether they affected the
opioid withdrawal response. 3.
Adenosine (1-5 microM), but not
U-50,488H (1-5 microM),
somatostatin (0.01-5 microM), ocreotide (1-5 microM),
baclofen (1-25 microM) or
dopamine (5, 50 microM), produced a
contracture on washout following 2 min contact with the ileum. The
adenosine (5 microM) washout
contracture, in common with MEnk and
noradrenaline washout
contractures, was inhibited by the
substance P antagonist,
spantide (10 microM). 4. Added 30 s before washout at a concentration of 5 microM,
noradrenaline,
U-50,488H,
adenosine,
somatostatin and ocreotide significantly inhibited the washout withdrawal response following 2 min contact of the ileum with MEnk, 1 microM. A higher concentration of
baclofen, 250 microM, also inhibited this response. 5. The
naloxone (1 microM)-precipitated withdrawal response following contact of the ileum with MEnk, 1 microM, for 2 min, was inhibited only by
noradrenaline (5 microM) and
U-50,488H (5 microM). 6. It is concluded that during
naloxone-precipitated
opioid withdrawal an additional population of enteric motor neurones is recruited which is not involved in the washout withdrawal response and these neurones have less diversity of
presynaptic receptors mediating inhibition of transmitter release than
cholinergic motor neurones.