NANC inhibitory neurotransmission in mouse isolated stomach: involvement of nitric oxide, ATP and vasoactive intestinal polypeptide.
1. The neurotransmitters involved in NANC relaxation and their possible interactions were investigated in mouse isolated stomach, recording the motor responses as changes of endoluminal pressure from whole organ. 2. Field stimulation produced tetrodotoxin-sensitive, frequency-dependent, biphasic responses: rapid transient relaxation followed by a delayed inhibitory component. 3. The inhibitor of the synthesis of nitric oxide (NO), l-NAME, abolished the rapid relaxation and significantly reduced the slow relaxation. Apamin, blocker of Ca2+-dependent K+ channels, or ADPbetaS, which desensitises P2y purinoceptors, reduced the slow relaxation to 2-8 Hz, without affecting that to 16-32 Hz or the fast relaxation. alpha-Chymotrypsin or vasoactive intestinal polypeptide 6-28 (VIP6-28), antagonist of VIP receptors, failed to affect the fast component or the delayed relaxation to 2-4 Hz, but antagonised the slow component to 8-32 Hz. 4. Relaxation to sodium nitroprusside was not affected by l-NAME, apamin or ADPbetaS, but was reduced by alpha-chymotrypsin or VIP6-28. Relaxation to VIP was abolished by alpha-chymotrypsin, antagonised by VIP6-28, but was not affected by l-NAME, apamin or ADPbetaS. Relaxation to ATP was abolished by apamin, antagonised by ADPbetaS, but was not affected by l-NAME or alpha-chymotrypsin. 5. The present results suggest that NO is responsible for the rapid relaxation and partly for the slow relaxation. ATP is involved in the slow relaxation evoked by low frequencies of stimulation. VIP is responsible for the slow relaxation evoked by high frequencies of stimulation. The different neurotransmitters appear to work in parallel, although NO could serve also as a neuromodulator that facilitates release of VIP.
Mulè
Flavia
F
Dipartimento di Biologia cellulare e dello Sviluppo, Università di Palermo - 90128, Palermo, Italia. fmule@unipa.it
Serio
Rosa
R
D000244:Adenosine Diphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000320:Adrenergic Fibers / Q000502:physiology; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D002799:Cholinergic Fibers / Q000502:physiology; D002918:Chymotrypsin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D009126:Muscle Relaxation / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D018005:Receptors, Vasoactive Intestinal Peptide / Q000037:antagonists & inhibitors / Q000502:physiology; D013270:Stomach / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*; D013873:Thionucleotides / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D018005:Receptors, Vasoactive Intestinal Peptide; D013873:Thionucleotides; D009599:Nitroprusside; D001030:Apamin; D009569:Nitric Oxide; C030812:adenosine 5'-O-(2-thiodiphosphate); D014660:Vasoactive Intestinal Peptide; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D019001:Nitric Oxide Synthase; D002918:Chymotrypsin; C117608:alpha-chymotrypsin; D019331:NG-Nitroarginine Methyl Ester