Regulation of VIP release from rat enteric nerve terminals: evidence for a stimulatory effect of NO.
The basal release of vasoactive intestinal polypeptide (VIP) from freshly prepared enriched synaptosomes was 159.1 +/- 17.3 fmol/mg protein (100%), which constituted 2.5% of the total VIP content. Basal VIP release was reduced by 65% by removal of external Ca2+. Release of VIP was stimulated by depolarization with KCl (65 mM, 143%) and in the presence of veratridine (10(-6) M, 184%), monensin (10(-5) M, 131%), and the Ca2+ ionophore A-23187 (10(-6) M, 160%). Stimulation of adenosine 3',5'-cyclic monophosphate (cAMP)-dependent mechanisms using isoproterenol (10(-6)-10(-4) M) and forskolin (10(-6) and 10(-5) M) had no stimulatory influence on VIP release. In contrast, sodium nitroprusside (10(-4) M, 198%), the nitric oxide (NO) donor 3-(morpholino)sydnonimine (10(-4) M, 155%), and the guanosine 3',5'-cyclic monophosphate (cGMP) analogue 8-bromo cGMP (10(-4) M, 196%) caused a significant release of VIP. L-Arginine (10(-3) M, 246%) also caused a significant increase of VIP release that was antagonized by the NO synthase inhibitor N omega-nitro-L-arginine methyl ester (5 x 10(-4) M, 131%), which had no effect when given alone. The results demonstrate that VIP can be released from enriched synaptosomes by Ca(2+)-dependent mechanisms by NO agonists or NO-dependent mechanisms. It is speculated that this VIP release is induced by a presynaptic stimulatory mechanism of NO and this effect could enhance or contribute to the action of NO.
Department of Internal Medicine II, Technical University of Munich, Germany. han.allescher@lrz.tu-muenchen.de
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Allescher
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Kurjak
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Huber
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D000818:Animals; D001120:Arginine / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D002458:Cell Fractionation / Q000379:methods; D006152:Cyclic GMP / Q000494:pharmacology; D007421:Intestine, Small / Q000294:innervation*; D008564:Membrane Potentials; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009252:NADPH Dehydrogenase / Q000378:metabolism; D009411:Nerve Endings / Q000378:metabolism; D009569:Nitric Oxide / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013574:Synaptosomes / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism*
D009599:Nitroprusside; D009569:Nitric Oxide; D014660:Vasoactive Intestinal Peptide; C002385:linsidomine; D001120:Arginine; D008981:Molsidomine; D009252:NADPH Dehydrogenase; D011493:Protein Kinase C; D006152:Cyclic GMP; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium