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  • Inhibitory neurotransmission  (2)
  • Cell migration  (1)
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  • 1
    ISSN: 1432-1912
    Keywords: Senktide ; SR 142,801 ; NANC ; Nitric oxide ; Inhibitory neurotransmission
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In urethane-anaesthetized rats, moderate colonic distension (0.5 ml) induced reflex rhythmic contractions (5 mm Hg amplitude and 1.1 cycles/min frequency). Senktide (1–10 nmol/kg, i.v.), a tachykinin NK3 receptor selective agonist, transiently suppressed distension-induced contractions. SR 142,801 (1–10 gmol/kg, i.v.), a non-peptide tachykinin NK3 receptor antagonist, had no effect on distension-induced contractions but prevented the inhibitory effect of senktide. Infusion of N-ω-nitro-1-arginine methyl esther hydrochloride (L-NAME, 20 μmol/ml/h, i.v.) increased the amplitude of colonic contractions and decreased the inhibitory effect of senktide. Hexamethonium (15 μmol/ml/h, i.v.) or atropine (1 μmol/ml/h, i.v.) inhibited the distension-induced contractions. In hexamethonium- or atropine-treated rats, senktide (10 nmol/kg) transiently and selectively enhanced the amplitude of contractions. Also SR 142,801 (10 μmol/kg), but not its inactive enantiomer SR 142,806, increased both amplitude and frequency of contractions. During continuous infusion of L-NAME and hexamethonium or atropine both frequency and amplitude of distension-induced colonic contractions were higher than when in hexamethonium or atropine only. Senktide (10 nmol/kg) had no effect and SR 142,801 (10 pmol/kg) produced a slight enhancement of colonic contractions. Infusion of sodium nitroprusside (3 μmol/ml/h, i.v.) decreased amplitude and frequency of distension-induced contractions. SR 142,801 had no effect in the presence of the nitric oxide (NO) donor. We conclude that tachykinins acting through NK3 receptors exert at least four different actions on colonic motility activated by distension: (1) a hexamethonium resistant, NO-dependent, suppressant effect on contractions; (2) a hexamethonium-sensitive, NO-independent inhibitory effect on the amplitude of contractions; (3) a hexamethonium-resistant, NO-independent inhibitory effect on the amplitude of contractions and (4) a hexamethonium resistant and L-NAME-sensitive excitatory effect on amplitude of contractions. The prevalent inhibitory effect evoked in normal conditions along with the excitatory activity induced by SR 142,801 on hexamethonium-resistant colonic motility indicates that tachykinins, acting through neuronal NK3 receptors, activate NO-dependent and NO-independent inhibitory neurotransmission in the rat colon.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 353 (1996), S. 475-481 
    ISSN: 1432-1912
    Keywords: Cell migration ; Substance P ; NK1 receptor ; Human skin fibroblasts
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Fibroblast migration is an important component of the tissue response during the repair process, and substance P (SP) has been shown to exert trophic effects. In the present study, cell migration was evaluated as the distance travelled by adherent human skin fibroblasts (HF) at 96 h and by the number of individual cells moving across a filter within 5 h. In control conditions (1% calf serum) adherent fibroblasts moved from the starting line by approximately 700 μm. The addition of SP (10−11–10−7 M) increased HF mobilisation in a concentration-dependent manner, with maximal activity at 10−8 M (50% increase in migration over control). Migration of individual HF in suspension was also promoted by SP in a concentration-dependent manner, with an EC50 of 2.2×10−9 M. The response produced by the maximally effective concentration of SP was equal to 65 and 90% of the effect elicited by 100 ng/ml Platelet-Derived Growth Factor AB (PDGF A/B) on adherent and individual cells respectively. The synthetic NK1 receptor agonist [Sar9]SP-sulphone (10−11–10−6 M) reproduced the SP effect. The NK2 and NK3 receptor agonists [βAla8]NKA(4–10) and [MePhe7]NKB were devoid of any effect. The effect of SP was antagonised by two selective antagonists of NK1 receptors, namely (±) CP 96,345 (10−10–10−8 M) and FK 888 (10−9–10−7 M), while the NK2 receptor antagonist MEN 10627 (10−8–10−7 M) was not effective. Our data indicate that SP is a potent effector of fibroblast migration and the NK1 receptor is responsible for this effect. These observations further support the specific role of the NK1 receptor in mediating the trophic function of SP at the cutaneous level.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1912
    Keywords: Key words Senktide ; SR 142 ; 801 ; NANC ; Nitricoxide ; Inhibitory neurotransmission
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In urethane-anaesthetized rats, moderate colonic distension (0.5 ml) induced reflex rhythmic contractions (5 mm Hg amplitude and 1.1 cycles/min frequency). Senktide (1–10 nmol/kg, i.v.), a tachykinin NK3 receptor selective agonist, transiently suppressed distension-induced contractions. SR 142,801 (1–10 μmol/kg, i.v.), a non-peptide tachykinin NK3 receptor antagonist, had no effect on distension-induced contractions but prevented the inhibitory effect of senktide.  Infusion of N-ω-nitro-1-arginine methyl esther hydrochloride (L-NAME, 20 μmol/ml/h, i.v.) increased the amplitude of colonic contractions and decreased the inhibitory effect of senktide.  Hexamethonium (15 μmol/ml/h, i.v.) or atropine (1 μmol/ml/h, i.v.) inhibited the distension-induced contractions. In hexamethonium- or atropine-treated rats, senktide (10 nmol/kg) transiently and selectively enhanced the amplitude of contractions. Also SR 142,801 (10 μmol/kg), but not its inactive enantiomer SR 142,806, increased both amplitude and frequency of contractions.  During continuous infusion of L-NAME and hexamethonium or atropine both frequency and amplitude of distension-induced colonic contractions were higher than when in hexamethonium or atropine only. Senktide (10 nmol/kg) had no effect and SR 142,801 (10 μmol/kg) produced a slight enhancement of colonic contractions.  Infusion of sodium nitroprusside (3 μmol/ml/h, i.v.) decreased amplitude and frequency of distension-induced contractions. SR 142,801 had no effect in the presence of the nitric oxide (NO) donor.  We conclude that tachykinins acting through NK3 receptors exert at least four different actions on colonic motility activated by distension: 1) a hexamethonium-resistant, NO-dependent, suppressant effect on contractions; 2) a hexamethonium-sensitive, NO-independent inhibitory effect on the amplitude of contractions; 3) a hexamethonium-resistant, NO-independent inhibitory effect on the amplitude of contractions and 4) a hexamethonium resistant and L-NAME-sensitive excitatory effect on amplitude of contractions. The prevalent inhibitory effect evoked in normal conditions along with the excitatory activity induced by SR 142,801 on hexamethonium-resistant colonic motility indicates that tachykinins, acting through neuronal NK3 receptors, activate NO-dependent and NO-independent inhibitory neurotransmission in the rat colon.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
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