TY - JOUR
T1 - Inhibitory effect of PACAP(6-38) on relaxations induced by PACAP, VIP and non-adrenergic, non-cholinergic nerve stimulation in the guinea-pig taenia caeci
AU - Lénárd, L.
AU - Lázár, Z.
AU - Benkó, R.
AU - Szigeti, R.
AU - Báthori, Z.
AU - Tóth, G. K.
AU - Penke, B.
AU - Barthó, L.
N1 - Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.
PY - 2000
Y1 - 2000
N2 - The effect of the pituitary adenylate cyclase activating polypeptide (PACAP) receptor antagonist PACAP(6-38) on the relaxant response to exogenous PACAP, vasoactive intestinal polypeptide (VIP) and nonadrenergic, non- cholinergic (NANC) nerve stimulation was tested in the guinea-pig taenia caeci, in the presence of atropine (10-6 M) and guanethidine (3x10-6 M). PACAP(6-38) (3x10-6 M) strongly inhibited sub-maximal relaxations evoked by exogenous PACAP (1-3x 10-8 M) or VIP (10-8 M), but not those due to isoprenaline (4-8x10-8 M) or ATP (10-6 M). PACAP(6-38) caused a small but significant (approximately 20%) inhibition of the NANC relaxation due to electrical field stimulation (1 Hz or 10 Hz for 20 s). At these frequencies PACAP(6-38) caused no inhibition of the NANC relaxation in the presence of the P2 purinoceptor antagonist pyridoxalphosphate-6-azophenyl-2',4'- disulphonic acid (PPADS; 5x10-5 M), or PPADS plus the NO-synthase blocker N(G)-nitro-L-arginine (L-NOARG; 10-4 M); in preparations pretreated with L- NOARG (10-4 M) alone PACAP(6-38) retained its inhibitory effect. The PPADS- and L-NOARG-resistant NANC relaxation with 10 Hz electrical stimulation was blocked by apamin (10-7 M); it was not significantly modified by the tachykinin receptor antagonist spantide (10-5 M). Tachyphylaxis to PACAP(1- 27) (10-7 M for 10 min) strongly inhibited the relaxation due to PACAP(1- 38) (1-3x10-8 M) and reduced electrical stimulation-evoked relaxations by half. The putative VIP antagonist VIP(10-28) (10-5 M) failed to significantly reduce the relaxant action of exogenous VIP (1-3x10-8 M). Relaxation induced by PACAP(1-38) (1-2x10-8 M) was not influenced by a mixture of PPADS (5x10-5 M) and L-NOARG (10-4 M). It is concluded that: (a) PACAP(6-38) is a VIP/PACAP antagonist in the guinea-pig taenia caeci; (b) a release of a VIP/PACAP-like substance from enteric nerves is involved in the NANC relaxation in this preparation, but its contribution is relatively small and seems to depend on the functional integrity of the PPADS-sensitive inhibitory mechanism; (c) the PPADS- plus L-NOARG-resistant NANC relaxation probably involves apamin-sensitive K+ channels.
AB - The effect of the pituitary adenylate cyclase activating polypeptide (PACAP) receptor antagonist PACAP(6-38) on the relaxant response to exogenous PACAP, vasoactive intestinal polypeptide (VIP) and nonadrenergic, non- cholinergic (NANC) nerve stimulation was tested in the guinea-pig taenia caeci, in the presence of atropine (10-6 M) and guanethidine (3x10-6 M). PACAP(6-38) (3x10-6 M) strongly inhibited sub-maximal relaxations evoked by exogenous PACAP (1-3x 10-8 M) or VIP (10-8 M), but not those due to isoprenaline (4-8x10-8 M) or ATP (10-6 M). PACAP(6-38) caused a small but significant (approximately 20%) inhibition of the NANC relaxation due to electrical field stimulation (1 Hz or 10 Hz for 20 s). At these frequencies PACAP(6-38) caused no inhibition of the NANC relaxation in the presence of the P2 purinoceptor antagonist pyridoxalphosphate-6-azophenyl-2',4'- disulphonic acid (PPADS; 5x10-5 M), or PPADS plus the NO-synthase blocker N(G)-nitro-L-arginine (L-NOARG; 10-4 M); in preparations pretreated with L- NOARG (10-4 M) alone PACAP(6-38) retained its inhibitory effect. The PPADS- and L-NOARG-resistant NANC relaxation with 10 Hz electrical stimulation was blocked by apamin (10-7 M); it was not significantly modified by the tachykinin receptor antagonist spantide (10-5 M). Tachyphylaxis to PACAP(1- 27) (10-7 M for 10 min) strongly inhibited the relaxation due to PACAP(1- 38) (1-3x10-8 M) and reduced electrical stimulation-evoked relaxations by half. The putative VIP antagonist VIP(10-28) (10-5 M) failed to significantly reduce the relaxant action of exogenous VIP (1-3x10-8 M). Relaxation induced by PACAP(1-38) (1-2x10-8 M) was not influenced by a mixture of PPADS (5x10-5 M) and L-NOARG (10-4 M). It is concluded that: (a) PACAP(6-38) is a VIP/PACAP antagonist in the guinea-pig taenia caeci; (b) a release of a VIP/PACAP-like substance from enteric nerves is involved in the NANC relaxation in this preparation, but its contribution is relatively small and seems to depend on the functional integrity of the PPADS-sensitive inhibitory mechanism; (c) the PPADS- plus L-NOARG-resistant NANC relaxation probably involves apamin-sensitive K+ channels.
KW - Non-adrenergic non-cholinergic (NANC) relaxation
KW - PACAP antagonist
KW - Pituitary adenylate cyclase activating polypeptide (PACAP)
KW - Taenia caeci (guinea pig)
KW - Vasoactive intestinal polypeptide (VIP)
KW - VIP antagonist
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U2 - 10.1007/s002100000225
DO - 10.1007/s002100000225
M3 - Article
C2 - 10832602
AN - SCOPUS:0034018016
VL - 361
SP - 492
EP - 497
JO - Naunyn-Schmiedeberg's Archives of Pharmacology
JF - Naunyn-Schmiedeberg's Archives of Pharmacology
SN - 0028-1298
IS - 5
ER -