vasoactive-intestinal-peptide and 7-nitroindazole

We have previously shown that kainic acid (KA) increases nitric oxide (NO) synthase (NOS) production in the rat dentate gyrus (DG) and hippocampus (CA3), and NOS inhibition [(by N(G)-nitro-L-arginine methylester (L-NAME)] modulates the vasoactive intestinal peptide (VIP)-responsive gene, activity-dependent neuroprotective protein, and alters neuro- and astrogliogenesis (Cosgrave et al. in Neurobiol Dis 30(3):281-292 2008, J Mol Neurosci 39(1-2):9-21, 2009, 2010). In the present study, using the same model we demonstrate that VIP synthesis is differentially regulated by the NO-cyclic guanosine monophosphate (cGMP) pathway in the DG and CA3 at 3 h and 3 days post-KA. At 3 h post-KA: In L-NAME+KA/7-nitroindazole (7-NI)+KA, stratum granulosum (SG) and subgranular zone (SGZ) cells were intensely stained for VIP when compared with L-NAME/7-NI/KA alone. Soluble guanylyl cyclase inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, blocks cGMP production), suppressed astrocytic activation (glial fibrillary acidic protein) but other cell types were VIP(+); however, ODQ+KA suppressed overall VIP synthesis in the DG. At 3 days post-KA: In L-NAME+KA/7-NI+KA, SGZ and SG cells continued to express VIP, while in the KA alone, only SGZ cells were VIP(+). ODQ increased VIP(+) cells in the SG, and in contrast to 3 h, VIP-containing nNOS(+) cells increased in ODQ+KA when compared to vehicle+KA. In the hippocampus, 7-NI/ODQ had no effect on VIP at 3 h/3 days, while L-NAME+KA at 3 days increased VIP(+) cells, but reduced VIP-like immunoreactivity in astrocytes. These results suggest that the NO-cGMP pathway differentially regulates VIP in the DG and hippocampus during seizure.

Topics: Animals; Cyclic GMP; Dentate Gyrus; Enzyme Inhibitors; Excitatory Amino Acid Agonists; Guanylate Cyclase; Hippocampus; Indazoles; Kainic Acid; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Synthase; Oxadiazoles; Quinoxalines; Rats; Rats, Wistar; Receptors, Cytoplasmic and Nuclear; Signal Transduction; Soluble Guanylyl Cyclase; Vasoactive Intestinal Peptide

Prolactin (PRL) and vasoactive intestinal polypeptide (VIP) mRNA levels were elevated in the brainstem of neuronal nitric oxide synthase (nNOS) gene knockout (KO) mice compared to the levels in nNOS control mice. In addition, PRL mRNA levels increased in the hypothalamus and the brainstem of nNOS control mice after administration of 7-nitro-indazole (7-NI), a relatively selective nNOS inhibitor. The results suggest that NO inhibits PRL. No differences in the genes measured were observed in inducible NOS KO mice.

Topics: Animals; Brain Stem; Gene Expression Regulation; Hypothalamus; Indazoles; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Nerve Tissue Proteins; Nitric Oxide Synthase; Nitric Oxide Synthase Type I; Prolactin; RNA, Messenger; Vasoactive Intestinal Peptide

The receptors for vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating peptide (PACAP) were characterised in vitro on rat colon longitudinal smooth muscle with adherent myenteric ganglia. VIP, PACAP-38 and PACAP-27 all caused concentration-dependent relaxations. PACAP-27 and PACAP-38 were equipotent, while VIP was less potent. Tetrodotoxin (10(-6) M), L-NAME (10(-4) M), 7-NINA (10(-5) M) and ODQ (3 x 10(-6) M) reduced the amplitude of the relaxatory responses to PACAP-38 but did not affect relaxations induced by VIP or PACAP-27. Apamin (10(-6) M) almost totally abolished the PACAP-27- and PACAP-38-induced relaxations, while VIP-induced relaxations were only slightly reduced. Tetraethylammonium (TEA) reduced VIP- but not PACAP-27-induced relaxations, while charybdotoxin was ineffective. Cross-desensitisation between PACAP-27, PACAP-38 and VIP could be revealed to some extent.. VIP, PACAP-27 and PACAP-38 are effective relaxants in rat colon longitudinal muscle. The receptors involved are classified as: (1) a neuronal PAC1 receptor localised on NO-synthesising neurones, the preferred ligand being PACAP-38. Activation of this receptor leads to an increased NO production. (2) A smooth muscle PAC1 receptor, the preferred ligand being PACAP-27. However, also PACAP-38 and, to a less extent, VIP activate this receptor. The relaxatory responses elicited by both PACAP-27 and PACAP-38 are abolished by apamin and thus mediated through small conductance Ca2+-activated K+ channels. (3) A VIP-specific receptor localised on smooth muscle cells. The mechanisms whereby this receptor elicits a relaxatory response involve, at least to some extent, TEA-sensitive K+ channels.

Topics: Animals; Apamin; Colon; Female; Indazoles; Muscle Relaxation; Muscle, Smooth; Myenteric Plexus; Neuropeptides; NG-Nitroarginine Methyl Ester; Nitric Oxide; Oxadiazoles; Pituitary Adenylate Cyclase-Activating Polypeptide; Quinoxalines; Rats; Rats, Sprague-Dawley; Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; Receptors, Pituitary Hormone; Receptors, Vasoactive Intestinal Peptide; Tetrodotoxin; Vasoactive Intestinal Peptide