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C Goso

Publications and source records attributed to C Goso.

25 records · Page 2Linked to original sources
PubMed1993

Vanilloid receptors in the urinary bladder: regional distribution, localization on sensory nerves, and species-related differences.

Using selective surgical ablations we have investigated the localization of vanilloid receptors (specific [3H] resiniferatoxin binding sites) on terminals of the pelvic, hypogastric, and pudendal nerves in the rat urinary bladder. Pelvic and hypogastric nerve resections resulted in 90% and 25% loss of specific [3H] resiniferatoxin (RTX) binding sites, respectively, whilst pudendic nerve resection had no measurable effect on the binding. In control animals, the density of vanilloid receptors was 1.7-fold higher in the neck than in the dome of the urinary bladder; the Bmax values were 57 +/- 8 and 34 +/- 7 fmol/mg protein, respectively. The binding characteristics of the vanilloid receptor were similar in the urinary bladder of the rat and mouse: Kd values were 87 +/- 15 and 61 +/- 11 pM, Bmax values were 37 +/- 2 and 60 +/- 10 fmol/mg protein, respectively. In contrast to the findings for the rat and mouse, in the urinary bladder of the guinea pig and the hamster the low level of specific [3H]RTX binding prevented the detailed characterization of vanilloid receptors. Nonetheless, at a fixed (60pM) concentration of [3H]RTX, specific binding both in the guinea pig and hamster urinary bladder was approximately 20% of that in the rat urinary bladder. In the urinary bladder of newborn rats, as in adults, a single class of specific [3H]RTX binding sites was found which bound RTX with an affinity of 110 +/- 20 pM and with a maximal binding capacity of 30 +/- 5 fmol/mg protein.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Characterization of a peripheral vanilloid (capsaicin) receptor in the urinary bladder of the rat.

Specific binding of [3H]resiniferatoxin (RTX) is thought to represent the vanilloid (capsaicin) receptor. In the present study, we have used this binding assay to identify for the first time a vanilloid receptor in the periphery and to compare it to central vanilloid receptors present in dorsal root ganglia (DRG) as well as in spinal cord of the rat. Rat urinary bladder membranes bound [3H]RTX with a Kd of 30 +/- 4 pM and a Bmax of 65 +/- 14 fmol/mg protein; the corresponding values were 19 +/- 3 pM and 104 +/- 14 fmol/mg protein in DRG, and 16 +/- 3 pM and 50 +/- 9 fmol/mg protein in spinal cord. Capsaicin inhibited [3H]RTX binding to membranes from urinary bladder, spinal cord, and DRG with similar potency (Ki values were 0.5 +/- 0.1 microM, 0.3 +/- 0.1, and 0.6 +/- 0.1 microM, respectively). Interestingly, [3H]RTX bound to urinary bladder in a non-cooperative fashion in contrast with the apparent positive cooperativity of [3H]RTX binding in both DRG and spinal cord (cooperativity index = 1.8 and 1.7, respectively). This finding suggests heterogeneity in the properties of the vanilloid receptors in the rat.

Animals↗
PubMed1993

Capsaicin-induced relaxation in the rat isolated external urethral sphincter: characterization of the vanilloid receptor and mediation by CGRP.

1. The potential role of capsaicin-sensitive nerves in the relaxation of the rat external urethral sphincter (REUS) was evaluated by demonstrating the existence of specific vanilloid (capsaicin) receptors and by investigating the sensory neurotransmitter(s) putatively involved in this relaxation. 2. Capsaicin (1 microM) relaxed REUS strips precontracted with noradrenaline (NA) (0.1 mM). This effect underwent desensitization and it was absent in preparations taken from adult capsaicin-pretreated rats. 3. Capsaicin-induced relaxation of NA-precontracted REUS was mimicked by calcitonin gene-related peptide (CGRP, 0.3-10 microM), but not by substance P (1 microM), vasoactive intestinal polypeptide (VIP, 1 microM), alpha-beta methylene ATP (10 microM), gamma-aminobutyric acid (GABA, 3 mM) or galanin (1 microM). A cross-tachyphylaxis between capsaicin (1 microM) and CGRP (1 microM) was observed. Both capsaicin and CGRP-induced relaxation were partially antagonized by the proposed CGRP antagonist, CGRP (8-37) (10 microM). 4. Electrical field stimulation (EFS, 2.5 Hz, 60 V, 1 ms, trains of 5 s every 5 min) of REUS evoked a contraction characterized by a largely adrenergic slowly developing tonic contraction with superimposed fast twitches due to the striated component of the strips. Both capsaicin (1 microM) and CGRP (0.01-1 microM) produced an almost complete inhibition of EFS-induced tonic contraction. A cross-tachyphylaxis between capsaicin and CGRP was observed. Furthermore, these inhibitory actions were unaffected by CGRP (8-37) (10 microM). 5. [3H]-resiniferatoxin displayed specific, saturable binding to rat urethral membranes. Data were consistent with a single site with a Kd of 105 pM and a Bmax of 40 fmol mg-1 protein. This binding was inhibited by capsaicin with a Ki of 0.6 microM and it was reduced by approximately 80% in preparations taken from rats that had undergone surgical ablation of the major pelvic ganglion 4 days earlier.6. In conclusion we have demonstrated the existence of vanilloid receptors on capsaicin-sensitive nerves innervating the rat urethra mainly through the major pelvic ganglion. The activation of this set of nerves could lead to a local release of CGRP that in turn elicits a remarkable urethral relaxation. Such a mechanism could be of relevance in physiological conditions to facilitate urine expulsion during micturition and in pathological conditions to help removal of noxious stimuli following mechanical/chemical irritation of the lower urinary tract.

Animals↗
PubMed1993

Competitive inhibition by capsazepine of [3H]resiniferatoxin binding to central (spinal cord and dorsal root ganglia) and peripheral (urinary bladder and airways) vanilloid (capsaicin) receptors in the rat.

Capsazepine was reported to block capsaicin- and resiniferatoxin (RTX)-induced responses both in vivo and in vitro with Schild plots suggesting a competitive mechanism of action. We have used the [3H]RTX binding assay, thought to represent the vanilloid (capsaicin) receptor, to explore the inhibitory mechanism of capsazepine at the receptor level in the rat. In competition assays, capsazepine inhibited [3H]RTX binding by spinal cord, dorsal root ganglion (DRG) and urinary bladder membranes with similar Ki values of 4.0 +/- 0.3, 3.5 +/- 0.5 and 5.0 +/- 1.0 microM (mean +/- S.E.M.; three determinations), respectively. By contrast, capsazepine was 35- to 50-fold more potent for inhibiting specific [3H]RTX binding in the airways (Ki = 0.12 +/- 0.02 microM; mean +/- S.E.M.; four determinations). In experiments in which the concentration of [3H]RTX was varied, 10 microM capsazepine reduced the affinity of the vanilloid receptor expressed by DRG and spinal cord membranes for [3H]RTX from 15 +/- 3 to 43 +/- 5 pM, and from 20 +/- 3 to 80 +/- 5 pM (mean +/- S.E.M.; three determinations), respectively, without a measurable change in Bmax or in cooperativity index; these shifts in affinity yield Ki values of 5.2 and 3.3 microM for DRG and spinal cord membranes, respectively. Capsaicin inhibited [3H]RTX binding by spinal cord, DRG and urinary bladder membranes with a 6- to 13-fold higher potency than did capsazepine; the Ki values were 0.3 +/- 0.1, 0.6 +/- 0.4 and 0.5 +/- 0.2 microM (mean +/- S.E.M.; three determinations), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Role of C-terminal amidation on the biological activity of neurokinin A derivatives with agonist and antagonist properties.

The mammalian tachykinins, neurokinin A (NKA) and NKA(4-10), along with the tachykinin NK2 receptor-selective antagonist MEN 10,376, were compared to their C-terminal free acid derivatives, NKA-OH, NKA(4-10)-OH and MEN 10,456, respectively, on several in vitro bioassays for NK1, NK2 and NK3 tachykinin receptors. NKA-OH and NKA(4-10)-OH were much weaker agonists than NKA or NKA(4-10) in the endothelium-deprived rabbit pulmonary artery (endowed with NK2A receptors) and in the guinea pig isolated bronchus (endowed with NK2A and NK1 receptors), where they produced submaximal contractile responses, and were inactive in the hamster isolated trachea (endowed with NK2B receptors) and in the rat isolated portal vein (endowed with NK3 receptors). At NK1 receptors of the guinea pig isolated ileum, NKA-OH produced weak agonist responses, whereas NKA(4-10)-OH was ineffective. In sharp contrast, MEN 10,456, while maintaining the same antagonist potency of the parent compound MEN 10,376 in the rabbit pulmonary artery and hamster isolated trachea, developed a clear-cut agonist character in the rat isolated portal vein, guinea pig isolated ileum and guinea pig isolated bronchus. The agonist responses produced by MEN 10,456 (10 microM) were reduced by MEN 10,376 in the guinea pig isolated bronchus and by the NK1 receptor antagonist GR 82,334 in the guinea pig isolated ileum. These results, although indicating the importance of C-terminal amidation for the agonist activity of natural tachykinins, suggest that the C-terminal amide group may not be directly involved in stimulation of the tachykinin receptors, but could induce agonist activity through a conformation effect.

Amides↗
PubMed1992

Effect of synthetic thymic humoral factor (THF-gamma 2) on T cell activities in immunodeficient ageing mice.

Immunodeficient ageing (C57BL/10 x DBA/2)F1 mice were treated by a single injection of synthetic thymic hormones and 4 days later their thymus and spleen cells were assayed in vitro for T cell activities. A few nanograms of THF-gamma 2 were found to raise the frequency of mitogen-responsive T cells in thymus and spleen cell populations as well as the frequency of cytokine-producing splenic T cells, up to the levels observed in young mice. Moreover, injection of THF-gamma 2 was found to restore T cell growth factor (TCGF) production by mitogen-stimulated spleen cells. Also, the helper activity of spleen cells was enhanced by this treatment and increased with increasing the THF-gamma 2 dose over a wide range. Similarly, the effects of thymopentin and thymosin-alpha 1 on T helper cell activity increased with increasing the injected dose, but the efficiencies of THF-gamma 2 and thymopentin were, respectively, 400-fold and eight-fold greater than that of thymosin-alpha 1.

Aging↗