Electrophysiological Evidence for Different Release Mechanism of ATP and NO As Inhibitory NANC Transmitters in Guinea-pig Colon
Overview
Authors
Affiliations
1. The effect of the P2-purinoceptor antagonist, suramin, the specific N-type voltage-dependent calcium channel blocker, omega-conotoxin GVIA (omega-CgTx) and the delta-opioid receptor agonist [D-Pen2,D-Pen5] enkephalin (DPDPE) on the apamin-sensitive and apamin-resistant inhibitory junction potentials (i.j.ps) produced by electrical field stimulation (EFS) were investigated by means of a sucrose-gap technique in the circular muscle of the guinea-pig colon. 2. After incubation of muscle strips in either atropine (1 microM), guanethidine (3 microM) and NG-nitro-L-arginine (L-NOARG, 30 microM) or atropine, guanethidine and apamin (0.3 microM), the addition of the NK1 receptor antagonist, SR 140,333 (1 microM) abolished the non-adrenergic, non-cholinergic (NANC) excitatory junction potential (e.j.p.) and unmasked a pure apamin-sensitive i.j.p. (in the presence of L-NOARG) or a pure apamin-resistant i.j.p. (in the presence of apamin). Both types of i.j.p. were abolished by tetrodotoxin. 3. Suramin (30-300 microM) concentration-dependently inhibited the apamin-sensitive i.j.p., while the apamin-resistant i.j.p. was not significantly affected by suramin (up to 300 microM). L-NOARG (30 microM) markedly reduced the apamin-resistant i.j.p. 4. The delta-opioid receptor agonist, DPDPE (0.03-3 microM) concentration-dependently reduced the apamin-sensitive i.j.p., while leaving the apamin-resistant i.j.p. unaffected. Naloxone (1 microM) prevented the i.j.p. inhibition evoked by DPDPE (0.3 microM). 5. omega-CgTx (0.3 microM) markedly reduced the apamin-sensitive but not the apamin-resistant i.j.p. The application of DPDPE (3 MicroM), after development of a steady state inhibitory effect by omega-CgTx, evoked further inhibition of the apamin-sensitive ij.p., similar to the effect produced by DPDPE alone. The L-type calcium channel blocker, nifedipine (1 MicroM) did not significantly affect either the apamin-sensitive or the apamin-resistant ij.ps.6. These findings support the purinergic origin of the fast, apamin-sensitive ij.p. produced by EFS in the circular muscle of the guinea-pig colon and strongly suggest that the apamin-sensitive and the apamin-resistant components of the evoked ij.p. utilize different mechanisms for the secretion of theNANC transmitters, ATP and NO, respectively.
Rodriguez-Tapia E, Naidoo V, DeVries M, Perez-Medina A, Galligan J Exp Physiol. 2016; 102(3):299-313.
PMID: 28008669 PMC: 5332280. DOI: 10.1113/EP086027.
Purinergic signalling in the gastrointestinal tract and related organs in health and disease.
Burnstock G Purinergic Signal. 2013; 10(1):3-50.
PMID: 24307520 PMC: 3944042. DOI: 10.1007/s11302-013-9397-9.
The in vitro pharmacological profile of TD-1211, a neutral opioid receptor antagonist.
Tsuruda P, Vickery R, Long D, Armstrong S, Beattie D Naunyn Schmiedebergs Arch Pharmacol. 2013; 386(6):479-91.
PMID: 23549670 DOI: 10.1007/s00210-013-0850-7.
Methylnaltrexone in the treatment of opioid-induced constipation.
Greenwood-Van Meerveld B, Standifer K Clin Exp Gastroenterol. 2011; 1:49-58.
PMID: 21677823 PMC: 3108626. DOI: 10.2147/ceg.s3889.
Matsuyama H, Thapaliya S, Takewaki T Br J Pharmacol. 1999; 128(3):830-6.
PMID: 10516669 PMC: 1571691. DOI: 10.1038/sj.bjp.0702851.