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Prejunctional modulation of non‐adrenergic non‐cholinergic (NANC) inhibitory responses in the isolated guinea‐pig gastric fundus
Author(s) -
Todorov S.,
Pozzoli C.,
Zamfirova R.,
Poli E.
Publication year - 2003
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1046/j.1365-2982.2003.00403.x
Subject(s) - chemistry , medicine , endocrinology , rauwolscine , hexamethonium , inhibitory postsynaptic potential , agonist , pharmacology , channel blocker , soluble guanylyl cyclase , stimulation , prazosin , receptor , biology , antagonist , biochemistry , guanylate cyclase , calcium
The inhibitory neurotransmission of the stomach was investigated in isolated guinea‐pig gastric fundus. In preparations treated with guanethidine (1 μ mol L −1 ) and p‐fluoro‐hexahydro‐sila‐difenidol (1 μ mol L −1 ), electrical stimulation evoked neurogenic inhibitory responses not modified by hexamethonium (100 μ mol L −1 ), suggesting that inhibitory postganglionic non‐adrenergic non‐cholinergic (NANC) nerve fibres are involved. The nitric oxide (NO)‐synthase inhibitor N ω ‐nitro‐ l ‐argininine‐methyl‐ester hydrochloride (1–100 μ mol L −1 ) and the soluble guanylyl cyclase inhibitor ODQ (0.1–3 μ mol L −1 ) also abolished such relaxant response, suggesting the involvement of NO/Cyclic Guanosine 3′,5′ monophosphate (cGMP) system as the final mechanism of muscle relaxation. The α 2 ‐adrenoceptor agonist, UK 14 304 (10 nmol L −1 –10 μ mol L −1 ) did not influence the electrical field stimulation (EFS)‐evoked NANC responses. These latter responses were also refractory to a variety of receptor agonists and antagonists, acting at Gamma Aminobutyric Acid (GABA), serotonin 5HT 1 a , opioid μ , δ and κ , muscarinic M 1 and M 2 , histamine H 2 and H 3 and cannabinoid receptors. The NANC response was insensitive to the P/Q‐type Ca 2+ ‐channel blocker ω ‐agatoxin TK (1 nmol L −1 –0.1 μ mol L −1 ), but partially inhibited by the N‐type Ca 2+ ‐channel blocker ω ‐conotoxin GVIA (0.1 nmol L −1 −0.1 μ mol L −1 ), and by the L‐type Ca 2+ ‐channel blockers nifedipine and calcicludine (0.1 nmol L −1 −0.1 μ mol L −1 ). These data suggest that the NANC relaxation of the isolated guinea‐pig gastric fundus is mediated by NO as the final inhibitory (neuro)transmitter at the longitudinal smooth muscle cells. The mechanism(s) promoting NO production is/are Ca 2+ ‐dependent, but apparently insensitive to presynaptic modulation. Both N‐ and L‐type channels seem to occur in nitrergic nerve endings, where they contribute to trigger NO diffusion at the synaptic cleft.