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Abstract

1,3-Di(2-tolyl)guanidine blocks nicotinic response in guinea pig myenteric neurons.

J J Galligan, B G Campbell, M P Kavanaugh, E Weber and R A North
Journal of Pharmacology and Experimental Therapeutics October 1989, 251 (1) 169-174;
J J Galligan
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B G Campbell
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M P Kavanaugh
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E Weber
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R A North
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Abstract

Ditolylguanidine (DTG) is a ligand which binds with high affinity to neuronal sigma receptors. Activation of sigma receptors inhibits the release of acetylcholine (ACh) from guinea pig ileum myenteric plexus preparations. A study was therefore undertaken to investigate the action of sigma receptor ligands on single neurons. Nicotinic responses to locally applied ACh onto single neurons of the guinea pig ileum myenteric plexus were studied using intracellular recording techniques. DTG and (+)-SKF10047 (N-allylnormetazocine) produced a concentration-dependent suppression of the depolarization of enteric neurons evoked by ionophoresis of ACh. The EC50 values for DTG and (+)-SKF10047 were 4.7 and 3.8 microM, respectively, and were similar to that for hexamethonium (3.2 microM). The inhibition of the ACh-depolarization was not mediated at sigma receptors because (-)SKF10047 and Bridge-DPG (2-imino-1,3H-dibenzo[d,f]-[1,3]-diazepine), which are inactive at sigma receptors, were as potent as DTG and (+)-SKF10047. DTG and hexamethonium (each at 1 microM) were more effective blockers of ACh-induced inward currents at a holding potential of -100 mV than at -40 mV. This voltage dependence is consistent with a channel blocking mechanism. DTG (10 microM) did not affect the depolarization (mediated by 5-HT3 receptors) induced by pressure application of 5-HT onto single neurons. DTG and Bridge-DPG inhibited contractures of the longitudinal muscle-myenteric plexus preparation elicited by dimethylphenylpiperazinium noncompetitively (EC50 values were 8.0 and 12.3 microM, respectively) whereas DTG but not Bridge-DPG inhibited 5-HT-induced contractions of the longitudinal muscle-myenteric plexus noncompetitively.(ABSTRACT TRUNCATED AT 250 WORDS)

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Journal of Pharmacology and Experimental Therapeutics
Vol. 251, Issue 1
1 Oct 1989
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Abstract

1,3-Di(2-tolyl)guanidine blocks nicotinic response in guinea pig myenteric neurons.

J J Galligan, B G Campbell, M P Kavanaugh, E Weber and R A North
Journal of Pharmacology and Experimental Therapeutics October 1, 1989, 251 (1) 169-174;

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Abstract

1,3-Di(2-tolyl)guanidine blocks nicotinic response in guinea pig myenteric neurons.

J J Galligan, B G Campbell, M P Kavanaugh, E Weber and R A North
Journal of Pharmacology and Experimental Therapeutics October 1, 1989, 251 (1) 169-174;
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