Characterizing voltage-dependent Ca(2+) channels coupled to VIP release and NO synthesis in enteric synaptosomes

• Published in: American journal of physiology: Gastrointestinal and liver physiology Vol. 283; no. 5; pp. G1027 - G1034
• Main Authors: Kurjak, M, Sennefelder, A, Aigner, M, Schusdziarra, V, Allescher, H D
• Format: Journal Article
• Language: English
• Published: United States 01.11.2002
• Subjects: Animals; Calcium Channel Blockers - pharmacology; Calcium Channels - metabolism; Intestine, Small - metabolism; Male; Nitric Oxide - biosynthesis; Nitric Oxide - pharmacology; Nitric Oxide Synthase - metabolism; Potassium - pharmacology; Rats; Rats, Wistar; Synaptosomes - metabolism; Vasoactive Intestinal Peptide - metabolism
• ISSN: 0193-1857; 1522-1547
• DOI: 10.1152/ajpgi.00400.2001

In enteric synaptosomes of the rat, the role of voltage-dependent Ca(2+) channels in K(+)-induced VIP release and nitric oxide (NO) synthesis was investigated. Basal VIP release was 39 +/- 4 pg/mg, and cofactor-substituted NO synthase activity was 7.0 +/- 0.8 fmol. mg(-1). min(-1). K(+) depolarization (65 mM) stimulated VIP release Ca(2+) dependently (basal, 100%; K(+), 172.2 +/- 16.2%; P < 0.05, n = 5). K(+)-stimulated VIP release was reduced by blockers of the P-type (omega-agatoxin-IVA, 3 x 10(-8) M) and N-type (omega-conotoxin-GVIA, 10(-6) M) Ca(2+) channels by ~50 and 25%, respectively, but not by blockers of the L-type (isradipine, 10(-8) M), Q-type (omega-conotoxin-MVIIC, 10(-6) M), or T-type (Ni(2+), 10(-6) M) Ca(2+) channels. In contrast, NO synthesis was suppressed by omega-agatoxin-IVA, omega-conotoxin-GVIA, and isradipine by ~79, 70, and 70%, respectively, whereas Ni(2+) and omega-conotoxin-MVIIC had no effect. These findings are suggestive of a coupling of depolarization-induced VIP release primarily to the P- and N-type Ca(2+) channels, whereas NO synthesis is presumably dependent on Ca(2+) influx not only via the P- and N- but also via the L-type Ca(2+) channel. In contrast, none of the Ca(2+) channel blockers affected VIP release evoked by exogenous NO, suggesting that NO induces VIP secretion by a different mechanism, presumably involving intracellular Ca(2+) stores.