Cholinergic responses of ileal longitudinal muscle under short-lasting exposure to cupric ions.

1 The effect of short-term exposure to cupric ions (Cu2+) on electric field-stimulated (EFS) or agonist-induced contractions of guinea-pig isolated ileum was studied. 2 EFS elicited tetrodotoxin- and atropine-sensitive contractions that were concentration dependently inhibited by Cu2+ (IC50 = 14.7 +/- 4.2 microm). Maximal inhibition (90.4 +/- 3.1% of baseline contractions) was attained with 30 microm Cu2+. 3 Carbachol induced concentration-dependent contractions (EC50 = 0.021 +/- 0.004 microm) that were inhibited by 0.3 microm atropine to a non-competitive manner (decreased maximal response, EC50 value = 0.26 +/- 0.04 microm, K(e) = 0.026 microm). Cu2+ (15 microm) potentiated contractions induced by carbachol, such that the maximum response was increased by 30.3 +/- 10.4%. 4 Histamine induced concentration-dependent contractions of the longitudinal muscle (EC50 = 0.11 +/- 0.03 microm). Dyphenhydramine (0.1 microm) decreased the maximum response to histamine and shifted the curve to the right (EC50 value = 4.71 +/- 0.35 microm, K(e) = 0.0024 microm). Cu2+ (15 microm) caused a rightward shift of the histamine concentration-response curve (EC50 = 0.61 +/- 0.1 microm) without changing the maximum response. Serotonin induced concentration-dependent contractions at concentrations higher than 10 nM (EC50 value of 0.34 +/- 0.12 microm) were not significantly affected by 15 microm Cu2+. 5 Our results suggest that in ileal longitudinal muscle, Cu2+ inhibits cholinergic neurotransmission but also facilitates postsynaptic muscarinic receptor responses.