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EFFECTS OF OPIOIDS ON NONCHOLINERGIC EXCITATORY RESPONSES OF THE GUINEA‐PIG ISOLATED ILEUM: INHIBITION OF RELEASE OF ENTERIC SUBSTANCE P
Author(s) -
GINTZLER ALAN R.,
SCALISI JENNIE A.
Publication year - 1982
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.1476-5381.1982.tb08773.x
Subject(s) - hexamethonium , chemistry , endocrinology , atropine , substance p , medicine , excitatory postsynaptic potential , ganglionic blocker , ileum , cholinergic , (+) naloxone , inhibitory postsynaptic potential , pharmacology , opioid , neuropeptide , receptor , biochemistry
1 Experiments were carried out to determine whether opiates and opioid peptides could affect noncholinergic excitatory responses of the isolated guinea‐pig ileum. 2 Transmural field stimulation (10–20 Hz) of an atropine pretreated, intact segment of gut produced a contracture that could be elicited repeatedly without significant variation in magnitude. 3 This noncholinergic contracture was significantly reduced 75.3 ±8.3% (mean±s.e.mean) by tetrodotoxin (TTX; 1 μg/ml) and by desensitizing the preparation to substance P (76.3 ± 10.1%). 4 Morphine (5 × 10 −6 m ) as well as the opioid peptides d ‐Ala 2 , N‐Phe 4 , Met‐(0)‐01 (FK 33–824; 9 × 10 −7 m ), d ‐Met 2 ‐Pro 5 enkephalin (3 × 10 −7 m ) and d ‐Ala 2 ‐ d ‐Leu 5 ‐enkephalin (5 × 10 −6 m ) inhibited the magnitude of the noncholinergic contracture but did not alter contractile responses to exogenous substance P (4 × 10 −11 m ‐4 × 10 −10 m ). 5 Pretreatment with the nicotinic receptor blocker, hexamethonium (10 −5 ‐10 −4 m ) reduced by about 35% the magnitude of the atropine‐resistant contracture but did not affect inhibitory responses to morphine or opioid peptides. Thus the inhibition produced by morphine on the 20 Hz contracture does not involve a nicotinic cholinergic mechanism. 6 Naloxone pretreatment (10 −6 m ) in the presence of hexamethonium (10 −5 ‐10 −4 m ) enhanced the magnitude of the noncholinergic contracture without affecting responses to exogenous substance P (4 × 10 −11 ‐4 × 10 −10 m ). 7 These data suggest that substance P is the main, if not the sole, mediator of the atropine‐resistant 20 Hz contracture and indicate further that exogenous as well as endogenous opioids can modulate the release of this enteric peptide.