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Effects of putative neurotransmitters and related drugs on withdrawal contractures of guinea‐pig isolated ileum following brief contact with [Met 5 ] enkephalin
Author(s) -
Chahl Loris A.
Publication year - 1990
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1990.tb14179.x
Subject(s) - chemistry , agonist , endocrinology , medicine , (+) naloxone , ileum , somatostatin , washout , adenosine , neurotransmitter , pharmacology , antagonist , anesthesia , receptor
1 Brief exposure for 2 min of guinea‐pig isolated ileum to [Met 5 ]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 μ m ), but not U‐50,488H (1–5 μ m ), somatostatin (0.01–5 μ m ), ocreotide (1–5 μ m ), baclofen (1–25 μ m ) or dopamine (5, 50 μ m ), produced a contracture on washout following 2 min contact with the ileum. The adenosine (5 μ m ) washout contracture, in common with MEnk and noradrenaline washout contractures, was inhibited by the substance P antagonist, spantide (10 μ m ). 4 Added 30 s before washout at a concentration of 5 μ m , noradrenaline, U‐50,488H, adenosine, somatostatin and ocreotide significantly inhibited the washout withdrawal response following 2 min contact of the ileum with MEnk, 1 μ m . A higher concentration of baclofen, 250 μ m , also inhibited this response. 5 The naloxone (1 μ m )‐precipitated withdrawal response following contact of the ileum with MEnk, 1 μ m , for 2 min, was inhibited only by noradrenaline (5 μ m ) and U‐50,488H (5 μ m ). 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.