Browsing by Author "LEWIN, J"

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    ENDOTHELIN-1 (ET)-INDUCED MOBILIZATION OF INTRACELLULAR CA2+ STORES FROM THE SMOOTH-MUSCLE FACILITATES SYMPATHETIC COTRANSMISSION BY POTENTIATION OF ADENOSINE 5'-TRIPHOSPHATE (ATP) MOTOR-ACTIVITY - STUDIES IN THE RAT VAS-DEFERENS
    (1992) DONOSO, MV; MONTES, CG; LEWIN, J; FOURNIER, A; CALIXTO, JB; HUIDOBROTORO, JP
    Endothelin-1 (ET) enhances nerve-stimulated contractions in epididymal (E) and prostatic (P) halves of the rat vas deferens, in addition to raising the basal tone in E. Whereas the peak increase in basal tone occurs in about 30 s, the maximal enhancement of neuro-transmission is observed within 5 min. The latter effect is long lasting is maintained even after extensive tissue washout. Furthermore, ET potentiates, in a concentration-dependent fashion, the adenosine 5'-triphosphate (ATP) or the adenylylimido-diphosphate (AMP-PNP) but not the noradrenaline (NA)-induced motor activity. The ATP motor response is partially blocked in media without Ca2+ plus 0.1 mM EGTA or following tissue incubation in buffer containing 10-50 nM nifedipine. However, these procedures do not modify significantly the ET-induced potentiation of the ATP contractions. The ET-induced potentiation of the ATP motor response is not modified by tissue preincubation in Ca2+-free buffer plus 10-30-mu-m ryanodine or 5-20 mM caffeine. The ET-induced rise in E basal tension is significantly reduced in the absence of external Ca2+ or by nifedipine; ryanodine does not modify this effect. Surgical denervation of the tissues does not obliterate the ET-induced potentiation of the ATP motor responses nor the ET increase in E basal tension in tissues superfused in Ca2+-free media or buffer with 2.5 mM Ca2+. Endothelin-1 does not significantly modify the overflow of H-3-NA, following transmural electrical depolarization of tissue nerve terminals. Hoe 140 did not interfere with the ET activity.
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    INVOLVEMENT OF ET(A) RECEPTORS IN THE FACILITATION BY ENDOTHELIN-1 OF NONADRENERGIC NONCHOLINERGIC TRANSMISSION IN THE RAT URINARY-BLADDER
    (1994) DONOSO, MV; SALAS, C; SEPULVEDA, G; LEWIN, J; FOURNIER, A; HUIDOBROTORO, JP
    1 Endothelin-l (ET-1; 3-10nM) raised the tone of rat bladders bathed in buffer containing atropine (1 mu M) plus guanethidine (3.4 mu M). In addition, ET-1 potentiated, in a concentration-dependent fashion (1-10nM), the contractions evoked by both transmural nerve stimulation and applications of exogenous adenosine 5'-triphosphate (ATP). 2 The threshold concentration of ET-1 required to facilitate non-adrenergic non-cholinergic (NANC) transmission and potentiate ATP-induced contractions, was about 10 fold lower than that required to increase the bladder tone (3nM). 3 The ET-l-induced increase in basal tension reached its maximal effect within 60-90s. In contrast, the 7.8 mu M ATP-induced contractions increased by 50% within the first minute following incubation with 10nM ET-1 but required about 5 min to develop the maximal effect. 4 The ET-l-induced potentiation of NANC or ATP responses was long-lasting and persisted in spite of extensive washing. The recovery of the bladder excitability depended on the concentration of ET-1. Following the application of 3nm ET-1, recovery required 30 min; applications of 10nM ET-1 required at least 60 min for full recovery. 5 The ET-1-induced potentiation of responses was selective for ATP and related structural analogues. ET-1 did not modify the contractions induced by acetylcholine, 5-hydroxytryptamine, prostaglandin F-2 alpha or bradykinin. 6 The potency of ET-2 was similar to that of ET-1. ET-3 and ET-C-terminal hexapeptide were inactive up to 100M. Sarafotoxin S6b was 2 to 3 fold less potent than ET-1 whereas sarafotoxin S6c (100nM) was inactive. AGETB-9 and AGETB-89, two ET(B) receptor agonists, were also inactive (up to 100nM). 7 Removal of one or both disulphide bonds in ET-1 and tryptophan-21 formylation of ET-1, resulted in inactive peptides (up to 100nM). 8 The ET-1 receptor antagonists, BE-18257B and FR139317, blocked both the ET-1-induced rise in tone and the potentiation of ATP responses in a concentration-dependent fashion. FR139317 was at least 30 fold more potent than BE-18257B. Both antagonists blocked at lower concentrations the ET-1 increase in bladder tone as compared to the ATP potentiation. The antagonism was slowly reversible. 9 Results are consistent with the presence of ET(A) receptors in the rat bladder, which mediate both actions of ET-1. The interaction of ET-1 with purinergic mechanisms is discussed.
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    PHARMACOLOGICAL CHARACTERIZATION OF ADENOSINE-A1 AND A2 RECEPTORS IN THE BLADDER - EVIDENCE FOR A MODULATORY ADENOSINE TONE REGULATING NONADRENERGIC NONCHOLINERGIC NEUROTRANSMISSION
    (1992) ACEVEDO, CG; CONTRERAS, E; ESCALONA, J; LEWIN, J; HUIDOBROTORO, JP
    1 The nerve-evoked contractions elicited by transmural electrical stimulation of mouse urinary bladders superfused in modified Krebs Ringer buffer containing 1-mu-M atropine plus 3.4-mu-M guanethidine were inhibited by adenosine (ADO) and related nucleoside analogues with the following rank order of potency: RB-phenylisopropyladenosine (RB-PIA) > cyclohexyladenosine (CHA) > 5'N-ethylcarboxamido adenosine (NECA) > ADO > S-phenylisopropyladenosine (S-PIA). Tissue preincubation with 8-phenyltheophylline (8-PT) displaced to the right, in a parallel fashion, the NECA concentration-response curve.