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Blockade of slow excitatory post‐synaptic potential by substance P antagonists in guinea‐pig sympathetic ganglia.
Author(s) -
Konishi S,
Otsuka M
Publication year - 1985
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.1985.sp015636
Subject(s) - substance p , mepyramine , endocrinology , medicine , depolarization , histamine , cholinergic , excitatory postsynaptic potential , antagonist , chemistry , biology , neuropeptide , inhibitory postsynaptic potential , receptor
The effects of three substance P (SP) antagonists on the inferior mesenteric ganglion of the guinea‐pig were studied using intracellular recording techniques, and the possible role of SP as a transmitter for the non‐cholinergic slow excitatory post‐synaptic potential (e.p.s.p.) was examined. The SP antagonist, [D‐Arg1, D‐Pro2, D‐Trp7,9, Leu11]SP, exerted a depolarizing action on the ganglion cells when applied by perfusion at a concentration of 3‐16 microM or by pressure ejection from a micropipette. This depolarizing action is probably due to a release of endogenous histamine because it was abolished by treatment with a histamine antagonist, mepyramine (1‐3 microM), or by a repeated application of the antagonist. When applied by pressure ejection, SP at 0.5‐1 microM depolarized the ganglion cells. In the presence of mepyramine, [D‐Arg1, D‐Pro2, D‐Trp7,9, Leu11]SP suppressed the SP‐induced depolarization by 41% at a concentration of 8 microM and by 75% at 16 microM. By contrast the SP antagonist did not affect the depolarizing action of angiotensin II on the ganglion cells. The non‐cholinergic slow e.p.s.p. evoked in the ganglion cells by repetitive stimulation of the lumbar splanchnic nerves was suppressed by [D‐Arg1, D‐Pro2, D‐Trp7,9, Leu11]SP at 8 or 16 microM. The degrees of suppression of both the non‐cholinergic slow e.p.s.p. and the SP‐induced depolarization by the SP antagonist were approximately equal. The cholinergic fast e.p.s.p. evoked by preganglionic nerve stimulation was not affected by the SP antagonist. [D‐Pro2, D‐Trp7,9]SP exhibited the properties of an SP antagonist similar to, but slightly weaker than [D‐Arg1, D‐Pro2, D‐Trp7,9, Leu11]SP. [D‐Pro2, D‐Phe7, D‐Trp9] at a concentration of 16 microM had a depolarizing action on the ganglion cells, which was not blocked by mepyramine. The peptide exerted hardly any antagonistic action against the SP‐induced depolarization of the ganglion cells. Stimulation of the other preganglionic (intermesenteric) nerves and the post‐ganglionic (colonic and hypogastric) nerves produced a non‐cholinergic slow e.p.s.p. in the inferior mesenteric ganglion cells. The non‐cholinergic slow e.p.s.p. evoked by both pre‐ and post‐ganglionic nerve stimulation were depressed by [D‐Arg1, D‐Pro2, D‐Trp7,9, Leu11]SP to similar extents. The present results show that [D‐Arg1, D‐Pro2, D‐Trp7,9, Leu11]SP and [D‐Pro2, D‐Trp7,9]SP can serve as specific SP antagonists in the inferior mesenteric ganglion of the guinea‐pig.(ABSTRACT TRUNCATED AT 400 WORDS)