Effect of GABA-ergic mechanisms on synaptosomal NO synthesis and the nitrergic component of NANC relaxation in rat ileum. 2011

M Kurjak, and J Fichna, and J Harbarth, and A Sennefelder, and H D Allescher, and V Schusdziarra, and M Storr, and B Otto
Endooffice Abdomen, Munich, Germany. manfred.kurjak@lrz.tum.de

BACKGROUND γ-Aminobutyric acid (GABA) acts on specific neural receptors [A, B and C(Aρ)] to modulate gastrointestinal function. The precise role of GABA receptor activation in the regulation of presynaptic nitric oxide (NO) synthesis in nerve terminals is unknown. METHODS Rat ileal nerve terminals were isolated by differential centrifugation. Nitric oxide synthesis was analysed using a L-[(3) H]arginine assay. In vitro studies were performed under non-adrenergic non-cholinergic (NANC) conditions on isolated ileal segments. RESULTS γ-Aminobutyric acid inhibited NO synthesis significantly (n = 6, P < 0.05) [(fmol mg(-1) min(-1)) control: 27.7 ± 1.5, 10(-6) mol L(-1): 19.7 ± 1.3; 10(-5) mol L(-1): 17.5 ± 3.0]. This effect was antagonized by the GABA A receptor antagonist bicuculline and the GABA C receptor antagonist (1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid (TPMPA), but not by the GABA B receptor antagonist SCH 50911. The GABA A receptor agonist muscimol [(fmol mg(-1) min(-1)) control: 27.6 ± 1.0, 10(-6) mol L(-1): 19.1 ± 1.7, n = 5, P < 0.05] and the GABA C receptor agonist cis-4-aminocrotonic acid (CACA) [(fmol mg(-1) min(-1)) control: 29.5 ± 3.2, 10(-3) mol L(-1): 20.3 ± 2.5, n = 6, P < 0.05], mimicked the GABA-effect, whereas the GABA B agonist baclofen was ineffective. Bicuculline reversed the inhibitory effect of muscimol, TPMPA antagonized the effect of CACA. In functional experiments the GABA A and C receptor agonists reduced the NANC relaxation induced by electrical field stimulation in rat ileum by about 40%. After NOS-inhibition by Nε-nitro-L-arginine methyl ester (L-NAME) the GABA A receptor agonist had no effect, whereas the GABA C receptor agonist still showed a residual response. CONCLUSIONS γ-Aminobutyric acid inhibits neural NO synthesis in rat ileum by GABA A and GABA C(Aρ) receptor-mediated mechanisms.

UI MeSH Term Description Entries
D007082 Ileum The distal and narrowest portion of the SMALL INTESTINE, between the JEJUNUM and the ILEOCECAL VALVE of the LARGE INTESTINE.
D008297 Male Males
D009126 Muscle Relaxation That phase of a muscle twitch during which a muscle returns to a resting position. Muscle Relaxations,Relaxation, Muscle,Relaxations, Muscle
D009130 Muscle, Smooth Unstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant. (From Stedman, 25th ed) Muscle, Involuntary,Smooth Muscle,Involuntary Muscle,Involuntary Muscles,Muscles, Involuntary,Muscles, Smooth,Smooth Muscles
D009569 Nitric Oxide A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP. Endogenous Nitrate Vasodilator,Mononitrogen Monoxide,Nitric Oxide, Endothelium-Derived,Nitrogen Monoxide,Endothelium-Derived Nitric Oxide,Monoxide, Mononitrogen,Monoxide, Nitrogen,Nitrate Vasodilator, Endogenous,Nitric Oxide, Endothelium Derived,Oxide, Nitric,Vasodilator, Endogenous Nitrate
D005680 gamma-Aminobutyric Acid The most common inhibitory neurotransmitter in the central nervous system. 4-Aminobutyric Acid,GABA,4-Aminobutanoic Acid,Aminalon,Aminalone,Gammalon,Lithium GABA,gamma-Aminobutyric Acid, Calcium Salt (2:1),gamma-Aminobutyric Acid, Hydrochloride,gamma-Aminobutyric Acid, Monolithium Salt,gamma-Aminobutyric Acid, Monosodium Salt,gamma-Aminobutyric Acid, Zinc Salt (2:1),4 Aminobutanoic Acid,4 Aminobutyric Acid,Acid, Hydrochloride gamma-Aminobutyric,GABA, Lithium,Hydrochloride gamma-Aminobutyric Acid,gamma Aminobutyric Acid,gamma Aminobutyric Acid, Hydrochloride,gamma Aminobutyric Acid, Monolithium Salt,gamma Aminobutyric Acid, Monosodium Salt
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013569 Synapses Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate via direct electrical coupling with ELECTRICAL SYNAPSES. Several other non-synaptic chemical or electric signal transmitting processes occur via extracellular mediated interactions. Synapse
D013574 Synaptosomes Pinched-off nerve endings and their contents of vesicles and cytoplasm together with the attached subsynaptic area of the membrane of the post-synaptic cell. They are largely artificial structures produced by fractionation after selective centrifugation of nervous tissue homogenates. Synaptosome
D017207 Rats, Sprague-Dawley A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company. Holtzman Rat,Rats, Holtzman,Sprague-Dawley Rat,Rats, Sprague Dawley,Holtzman Rats,Rat, Holtzman,Rat, Sprague-Dawley,Sprague Dawley Rat,Sprague Dawley Rats,Sprague-Dawley Rats

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