Dual actions of S-nitrosylated derivative of vasoactive intestinal peptide as a vasoactive intestinal peptide-like mediator and a nitric oxide carrier.

Published

Journal Article

Vasoactive intestinal peptide (VIP) has been postulated as a non-adrenergic non-cholinergic (NANC) transmitter in the relaxation of vascular and non-vascular systems. In order to synergize the vasoactivities of VIP with nitric oxide (NO), we synthesized a S-nitrosylated derivative of VIP, VIP-Gly-Cys-NO (VIPGC-NO). On aortic rings, VIPGC-NO exhibited a dose-dependent vasorelaxation similar to S-nitrosoglutathione (GSNO), and both induced complete vasorelaxation at 1 microM, whereas, VIP at 1 microM only produced 19% relaxation. The degree of vasorelaxation was proportional to the increases in cyclic GMP with no significant enhancement in cyclic AMP (cAMP) level. On precontracted tracheal rings, VIP, VIPGC-NO, VIPGC and GSNO produced relaxation with EC50 of 74+/-5, 32+/-6, 59+/-9, and 251+/-32 nM, respectively, which was consistent with increases in cyclic GMP (cGMP). A marked increase in cAMP was observed from the tracheal rings pretreated with VIP, VIPGC-NO and its parent VIP-Gly-Cys (VIPGC) as well as isoproterenol. Propranolol only blocked the airway relaxation induced by isoproterenol, but did not antagonize the relaxation induced by VIP, VIPGC and VIPGC-NO. On rabbit sphincter of Oddi, VIP, VIPGC-NO and VIPGC inhibited both basic and acetylcholine-induced contraction frequency and amplitude, whereas, GSNO was less potent than VIP and its derivatives over a range of 2 log units in this respect. On rat gastric fundus, these compounds inhibited contraction amplitude and frequency induced with 5-hydroxytryptamine (5-HT) in the order of inhibitory potency VIP > VIPGC-NO > VIPGC > isoproterenol > GSNO. Our data suggest that: (1) NO is selective in relaxing vascular smooth muscle via the cGMP pathway, whereas VIP is selective in relaxing non-vascular smooth muscles via the activation of both cGMP and cAMP pathways; (2) VIPGC-NO preserves the intrinsic function of VIP but acquires NO-like vasoactivities.

Full Text

Duke Authors

Cited Authors

  • Jia, L; Stamler, JS

Published Date

  • January 29, 1999

Published In

Volume / Issue

  • 366 / 1

Start / End Page

  • 79 - 86

PubMed ID

  • 10064155

Pubmed Central ID

  • 10064155

International Standard Serial Number (ISSN)

  • 0014-2999

Digital Object Identifier (DOI)

  • 10.1016/s0014-2999(98)00921-2

Language

  • eng

Conference Location

  • Netherlands