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The motor effect of the capsaicin-sensitive inhibitory innervation of the rat ureter
No full textNeurokinins activate TTX-insensitive rhythmic contractions of the rat isolated ureter. Field stimulation or capsaicin (1-3 uM) transiently inhibited the neurokinin-activated motility in controls but not capsain-pretreated (50 mg/kg sc) rats. The inhibitory action of field stimulation but not that of caspaicin was prevented by TTX. Thus a capsaicin-sensitive inhibitory innervation exists in the rat ureter
Facilitation of reflex micturition by intravesical administration of [βAla8]-neurokinin A (4-10), a selective NK-2 tachykinin receptor agonist
No full textThe ability of a selective agonist for NK-2 tackhykinin receptors to stimulate micturition in anaesthetised rats and guinea-pigs was investigated.
In both species, the intravesical instillation of the peptide at uM concentrations reduced bladder capacity and residual volume, indicating a facilitatory effect on reflex micturition, whereas no plasma extravasation was produced as determined by Evans Blue leakage.
In experiments on the isolated rat or guinea-pig bladder strips, the peptide induced powerful contractions. In a in vitro model of the guinea-pig whole bladder the intravesical instillation of the agonist facilitated the occurrence of rhythmic contractile activity.
The selective NK-2 receptor agonist is likely able to cross the urothelium and stimulate smooth muscle contraction
Visceromotor responses to calcitonin gene-related peptide (CGRP) in the rat lower urinary tract: evidence for a transmitter role in the capsaicin-sensitive nerves of the ureter
No full textLittle effects of CGRP were recorded on urinary bladder motility or plasma extravation. Otherwise, CGRP inhibited motility of isolated rat proxinal urethra and ureters and counteracted the contractile response to neurokinins. Edivence is provided that CGRP is able to influence the motility of the rat lower urinary tract, but exhibits marked regional differences. Endogenous CGRP could be the the inhibitory neurotransmitter which, when released from capsaicin-sensitive fibres, participate in the control of ureteral motility
Species-related variations in the effects of capsaicin on urinary bladder functions: relation to bladder content of substance P-like immunoreactivity
No full text1. The effect of capsaicin on bladder motility in vivo (urethane anaesthesia) and in vitro, plasma extravasation (Evans blue leakage technique) and content of substance P-like immunoreactivity (SP-LI) of the urinary bladder was investigated in various mammalian species. 2. Systemic capsaicin desensitization (rat and hamster, 50 mg/kg s.c. 4 days before; guinea-pig 55 mg/kg s. c. 4-7 days before) increased bladder capacity in rats and guinea-pigs and reduced voiding efficiency in guinea-pigs. All other urodynamic parameters were unaffected in both rats, guinea-pigs and hamsters. 3. Reflex bladder voiding was abolished by spinal cord transection in anaesthetized rats and hamsters. On the other hand, hexamethonium-(20 mg/kg i.v.)sensitive voiding contractions were obtained in response to saline filling 45 min from cord transection in guinea-pigs, indicating a profound interspecies variation in the basic organization of micturition. 4. Exposure to capsaicin (1 μM) produced a contraction of..
Further studies on the mechanisms of the tachykinin-induced activation of micturition reflex in rats: evidence for the involvement of the capsaicin-sensitive bladder mechanoreceptors
No full textThe relative ability of substance P, neurokinin A, neurokinin B and kassinin to activate the micturition reflex was investigated in urethane-anaesthetized rats. When administered topically neurokinin A, neurokinin B and kassinin were 14, 36 and 280 times, respectively, more potent than substance P to activate micturition. On the other hand substance P, neurokinin A and kassinin were practically equipotent (and neurokinin B was about 3-4 times less potent than substace P) to stimulate the contraction of the rat isolated bladder and to potentiate the contractions induced by electrical field stimulation. This indicates that neither a direct action on muscle cells nor a potentiating effect on efferent neurotransmission can account for the rank order of potency of tachykinins for activation of the micturition reflex. The ability of topical tachykinins to activate the micturition reflex was largely impaired in 2 months old rats pretreated with capsaicin (50 mg/kg s.c.) on their second day of..
Calcitonin gene-related peptide selectively increases cAMP levels in the guinea-pig ureter
No full textCalcitonin gene-related peptide (CGRP, 0.1 microM) and forskolin (10 microM) both produced a time-dependent accumulation of cAMP in homogenates of the guinea-pig ureter, while cromakalim (3 microM) was ineffective. Neither agent did increase the cGMP levels. cAMP accumulation induced by CGRP or forskolin was unchanged by glibenclamide (1 microM). In sucrose gap, the application of forskolin (1-10 microM for 15 s) hyperpolarized the smooth muscle membrane and its effect was greatly enhanced when tested in a low-K+ medium (extracellular K+ reduced from 5.9 to 1.2 mM). The hyperpolarization produced by 10 microM forskolin was reduced and abolished by 1 and 10 microM glibenclamide, respectively, in both normal and low-K+ medium. The present findings demonstrate that CGRP determines a selective cAMP accumulation in the guinea-pig ureter and suggest that elevation of cAMP may be involved in the opening of glibenclamide-sensitive K+ channels in the ureter smooth muscle
Regional differences in the effects of capsaicin and tachykinins on motor activity and vascular permeability in the rat lower urinary tract.
No full text1. The effects of capsaicin, substance P (SP) and neurokinin A (NKA) on motor activity and vascular permeability was investigated in the rat lower urinary tract (bladder dome and neck, proximal urethra and ureters). 2. Capsaicin produced contractions of the rat bladder dome and neck and of the proximal urethra in vitro, which were unaffected by tetrodotoxin and abolished by ganglionectomy. SP and NKA were almost equipotent in producing a contraction of the rat isolated bladder dome or neck and urethra. However, the maximal response to NKA was about twice that of SP on the urethra and bladder neck. 3. Capsaicin did not affect motility of the unstimulated rat isolated ureter, while NKA or SP activated rhythmic contractions, NKA being about 850 times more potent than SP. Either capsaicin or field stimulation produced a transient inhibition of the NKA-activated rhythmic contractions of the rat isolated ureter which was prevented by capsaicin-desensitization. 4. The capsaicin-(1 μM) or fiel..
The contribution of sensory nerves to xylene-induced cystitis in rats
No full textThe role of capsaicin-sensitive sensory nerves of the rat urinary bladder in xylene-induced cystitis was investigated. Instillation of xylene into the urinary bladder of female rats induced cystitis, e.g. detrusor hyperreflexia and increased vascular permeability. Detrusor hyperreflexia was also observed in rats desensitized to capsaicin as adults (50-125 mg/kg s.c., 4 days before) but only for a short period (1 h) after instillation. When a longer time lag (24 h) was allowed to elapse following instillation, reflex micturition was almost abolished. In rats desensitized to capsaicin as newborns (50 mg/kg s.c. on second day of life) reflex micturition was almost abolished and xylene (given 1 h before measurement) was ineffective. The xylene-induced plasma extravasation was greater in the bladder neck than in the dome. In the bladder neck the "early" response to xylene was reduced but not abolished in rats desensitized to capsaicin as adults or pretreated with compound 48 80 and was abolished in rats desensitized to capsaicin as newborns. The bladder content of substance P-like immunoreactivity decreased at various times following xylene instillation but this change occurred in parallel to the increase in bladder weight. These findings indicate that xylene-induced cystitis involves, at least in part, an irritation of capsaicin-sensitive sensory nerves in the bladder wall. The present results further suggest that xylene acts by stimulating at least two populations of sensory nerves which differ in their sensitivity towards capsaicin
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