Tachykinins as mediators of slow EPSPs in guinea-pig gall-bladder ganglia: involvement of neurokinin-3 receptors
1. The effects of endogenous tachykinins and related peptides on intact guinea-pig gall-bladder neurones were investigated with single-electrode voltage- and current-clamp recording techniques. 2. Pressure ejection of substance P (100 microM) caused a long lasting membrane depolarization that was as...
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Published in | The Journal of physiology Vol. 485; no. Pt 2; pp. 513 - 524 |
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Main Author | |
Format | Journal Article |
Language | English |
Published |
England
The Physiological Society
01.06.1995
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Subjects | |
Online Access | Get full text |
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Summary: | 1. The effects of endogenous tachykinins and related peptides on intact guinea-pig gall-bladder neurones were investigated
with single-electrode voltage- and current-clamp recording techniques. 2. Pressure ejection of substance P (100 microM) caused
a long lasting membrane depolarization that was associated with a decrease in input resistance. In cells that were voltage-clamped
to their resting membrane potential, substance P activated an inward current. 3. The reversal potentials of the substance
P-induced depolarization and inward current were congruent to 0 mV. In a low-Na+ solution, the substance P-induced depolarization
and inward current were reduced in amplitude. 4. Substance P increased the excitability of neurones, as evidenced by a greater
anodal break activity and an increase in the number of action potentials generated during a depolarizing current pulse. 5.
Substance P, neurokinin A (NKA) and neurokinin B (NKB) were applied by superfusion to determine the relative potencies of
these tachykinins. NKB was the most potent, with an EC50 of 24 nM. The EC50 values for NKA and substance P were 47.8 and 281
nM, respectively. 6. The neurokinin-3 (NK-3) receptor agonist senktide depolarized neurones with an EC50 of 6.3 nM. Neither
the NK-1 receptor agonist [Sar9,Met(O2)11]-substance P nor the NK-2 receptor agonist [beta-Ala8]-NKA(4-10) caused a measurable
depolarization. 7. The NK-3 antagonist [Trp7,beta-Ala8]-NKA (4-10) inhibited the responsiveness of gall-bladder neurones to
substance P with a KB (dissociation constant of receptor antagonist) of 49 nM, and depressed both capsaicin-induced depolarizations
and stimulus-evoked slow EPSPs. 8. These data indicate that tachykinins mediate slow EPSPs in guinea-pig gall-bladder ganglia
by activating NK-3 receptors on gall-bladder neurones. It is proposed that in response to inflammation or high intraluminal
pressure, tachykinins may be released within ganglia by sensory fibres and act directly on intrinsic neurones to facilitate
ganglionic transmission. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0022-3751 1469-7793 |
DOI: | 10.1113/jphysiol.1995.sp020747 |