Lénárd L, Lázár Z, Benkó R, Szigeti R, Báthori Z, Tóth G K, Penke B, Barthó L
Department of Pharmacology and Pharmacotherapy, University of Pécs Medical School, Hungary.
Naunyn Schmiedebergs Arch Pharmacol. 2000 May;361(5):492-7. doi: 10.1007/s002100000225.
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 pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS; 5x10(-5) M), or PPADS plus the NO-synthase blocker NG-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.
在豚鼠盲肠带中，于存在阿托品（10⁻⁶ M）和胍乙啶（3×10⁻⁶ M）的情况下，测试了垂体腺苷酸环化酶激活多肽（PACAP）受体拮抗剂PACAP(6 - 38)对外源性PACAP、血管活性肠肽（VIP）及非肾上腺素能、非胆碱能（NANC）神经刺激所引起的舒张反应的影响。PACAP(6 - 38)（3×10⁻⁶ M）强烈抑制外源性PACAP（1 - 3×10⁻⁸ M）或VIP（10⁻⁸ M）诱发的次最大舒张，但不抑制异丙肾上腺素（4 - 8×10⁻⁸ M）或ATP（10⁻⁶ M）所致的舒张。PACAP(6 -
