Prejunctional modulation of non-adrenergic non-cholinergic (NANC) inhibitory responses in the isolated guinea-pig gastric fundus.
The inhibitory neurotransmission of the stomach was investigated in isolated guinea-pig gastric fundus. In preparations treated with guanethidine (1 micro mol L-1) and p-fluoro-hexahydro-sila-difenidol (1 micro mol L-1), electrical stimulation evoked neurogenic inhibitory responses not modified by hexamethonium (100 micro mol L-1), suggesting that inhibitory postganglionic non-adrenergic non-cholinergic (NANC) nerve fibres are involved. The nitric oxide (NO)-synthase inhibitor Nomega-nitro-l-argininine-methyl-ester hydrochloride (1-100 micro mol L-1) and the soluble guanylyl cyclase inhibitor ODQ (0.1-3 micro 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 alpha2-adrenoceptor agonist, UK 14 304 (10 nmol L-1-10 micro 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 5HT1a, opioid micro , delta and kappa, muscarinic M1 and M2, histamine H2 and H3 and cannabinoid receptors. The NANC response was insensitive to the P/Q-type Ca2+-channel blocker omega-agatoxin TK (1 nmol L-1-0.1 micro mol L-1), but partially inhibited by the N-type Ca2+-channel blocker omega-conotoxin GVIA (0.1 nmol L-1-0.1 micro mol L-1), and by the L-type Ca2+-channel blockers nifedipine and calcicludine (0.1 nmol L-1-0.1 micro 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 Ca2+-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.
Todorov
S
S
Department of Physiology, Bulgarian Academy of Sciences, Sofia, Bulgaria.
Pozzoli
C
C
Zamfirova
R
R
Poli
E
E
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism; D004558:Electric Stimulation; D017615:Enteric Nervous System / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004837:Epinephrine / Q000378:metabolism; D005748:Gastric Fundus / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D006168:Guinea Pigs; D008297:Male; D009130:Muscle, Smooth / Q000378:metabolism; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology*; D009433:Neural Inhibition / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D009924:Organ Culture Techniques; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D009638:Norepinephrine; D004837:Epinephrine