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Electrophysiological evidence for different release mechanism of ATP and NO as inhibitory NANC transmitters in guinea‐pig colon
Author(s) -
Zagorodnyuk Vladimir,
Maggi Carlo Alberto
Publication year - 1994
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1994.tb13193.x
Subject(s) - apamin , chemistry , guanethidine , tetrodotoxin , medicine , endocrinology , agonist , nitroarginine , suramin , potassium channel , pharmacology , stimulation , receptor , biology , nitric oxide synthase , nitric oxide , biochemistry
1 The effect of the P 2 ‐purinoceptor antagonist, suramin, the specific N‐type voltage‐dependent calcium channel blocker, ω‐conotoxin GVIA (ω‐CgTx) and the δ‐opioid receptor agonist [ d ‐Pen 2 , d ‐Pen 5 ] 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 μ m ), guanethidine (3 μ m ) and N G ‐nitro‐ l ‐arginine ( l ‐NOARG, 30 μ m ) or atropine, guanethidine and apamin (0.3 μ m ), the addition of the NK 1 receptor antagonist, SR 140,333 (1 μ m ) 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 μ m ) 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 μ m ). l ‐NOARG (30 μ m ) markedly reduced the apamin‐resistant i.j.p. 4 The δ‐opioid receptor agonist, DPDPE (0.03–3 μ m ) concentration‐dependently reduced the apamin‐sensitive i.j.p., while leaving the apamin‐resistant i.j.p. unaffected. Naloxone (1 μ m ) prevented the i.j.p. inhibition evoked by DPDPE (0.3 μ m ). 5 ω‐CgTx (0.3 μ m ) markedly reduced the apamin‐sensitive but not the apamin‐resistant i.j.p. The application of DPDPE (3 μ m ), after development of a steady state inhibitory effect by ω‐CgTx, evoked further inhibition of the apamin‐sensitive i.j.p., similar to the effect produced by DPDPE alone. The L‐type calcium channel blocker, nifedipine (1 μ m ) did not significantly affect either the apamin‐sensitive or the apamin‐resistant i.j.ps. 6 These findings support the purinergic origin of the fast, apamin‐sensitive i.j.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 i.j.p. utilize different mechanisms for the secretion of the NANC transmitters, ATP and NO, respectively.