Potent contractile activity of endothelin on the human isolated urinary bladder

Maggi, Carlo Alberto; Giuliani, Sandro; Patacchini, Riccardo; Santicioli, Paolo; Turini, Damiano; Barbanti, Gabriele; Meli, Alberto

doi:10.1111/j.1476-5381.1989.tb11879.x

Cited by 62 publications

(31 citation statements)

References 7 publications

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“…In accordance with our previous findings (Maggi et al, 1989a), nifedipine (1 .M for 30mn) abolished the contractile response to KCI but had no significant effect on the response to endothelin (Figures 1 and 2). Carbachol-or neurokinin A-induced contractions were inhibited by nifedipine, the effect being more evident at low concentrations of the agonists.…”

Section: Effect Of Nifedipinesupporting

confidence: 80%

“…A second concentration-response curve to these agonists, made 45min after the first one gave reproducible results (n = 3 each, data not shown). By contrast, the effect of endothelin was difficult to remove by washing (Maggi et al, 1989a). …”

Section: Generalmentioning

confidence: 99%

“…In vivo studies in anaesthetized rats suggested that Ca mobilization via nifedipineresistant pathways might be a relevant mode of contraction during a physiological-like event, that is, volume-evoked bladder voiding (micturition reflex) (Maggi et al, 1988a). Fovaeus et al (1987) investigated the effect of nifedipine and Bay K 8644 on carbachol-induced contractions of human isolated bladder muscle and concluded that both voltagedependent and receptor-operated Ca channels mediate this response. Recently we studied the effect of endothelin, an endothelium-derived vasconstrictor peptide proposed to act as an endogenous agonist at dihydropyridine-sensitive Ca channels in the human isolated bladder (Maggi et al, 1989a) and found that the contractile response to this peptide was almost totally nifedipine-resistant while the KCI-induced contraction was abolished by nifedipine-pretreatment. These observations prompted us to re-address N02/02 (1/2) and halothane (0.6-1 %).…”

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confidence: 99%

“…Tissues were placed in icecold physiological salt solution within 2-3 min from surgical removal. Most experiments were performed on strips which were stored overnight in ice-cold physiological salt solution and continuously gassed with 96% 02 and 4% CO2 as described previously (Maggi et al, 1988b;1989a). Some experiments were performed within 3 h of surgery ('fresh' strips).…”

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Multiple sources of calcium for contraction of the human urinary bladder muscle

Maggi

Giuliani

Patacchini

et al. 1989

British J Pharmacology

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1 KC1, carbachol, neurokinin A and endothelin produced concentration-dependent contractions of mucosa-free muscle strips from the dome of the human urinary bladder. The maximal response to carbachol or neurokinin A exceeded that to KCI, while the maximal response to endothelin approached that to KCI.2 Nifedipine (1 gM) abolished the response to KCI, reduced the response to carbachol or neurokinin A but had no effect on the response to endothelin. Bay K 8644 (1 gM) markedly potentiated the response to KCl but had little or no effect on the response produced by the other stimulants. 3 Superfusion of the strips with a nominally calcium (Ca)-free medium containing EDTA (1 mM) for 30min markedly reduced the response to carbachol, neurokinin A and endothelin, although a small response was still evident at high concentrations. Likewise, after a prolonged (60min) superfusion of the strips with a high K (80mM) Ca-free medium plus EDTA (1 mM) these three agonists still produced a small contractile response.4 The nifedipine (1 gM) resistant response to carbachol, neurokinin A or endothelin was markedly depressed by LaCl3 (1 mM). In contrast, the nifedipine-(1 gM) resistant response to carbachol was not modified by NiCl2 (0.1 mM) or co-conotoxin (0.1 Mm). 5 Caffeine produced divergent effects depending upon the temperature of incubation: a relaxation at 370C-and a concentration-dependent (2.5-20mM) contraction at 250C. The latter was markedly inhibited by procaine (3mM) but unaffected by nifedipine (1 gM).6 After a prolonged (60 min) superfusion with a high K, Ca-free medium containing EDTA the response to carbachol (100 Mm) was abolished by previous exposure to procaine (3mM). Conversely, the response to endothelin (1 MM) was unaffected by procaine. The response to endothelin in these experimental conditions was also resistant to LaCl3 (1 mM).7 These findings indicate that multiple sources of Ca age mobilized for contraction of the human bladder muscle by different stimulants. Dihydropyridine-and voltage-sensitive Ca channels provide the major if not the sole source of Ca for the response to KCI, play some role in the response to muscarinic (carbachol) or NK-2 tachykinin receptor stimulation but are not involved in the response to endothelin. Carbachol, neurokinin A and endothelin all mobilize a Ca pool (either extracellular or located at membrane level) which is LaCl3-sensitive but nifedipine-resistant. Neither T-nor N-type channels appear to be involved in the response to carbachol. In addition, these agents mobilize a tightly bound Ca pool independently from membrane depolarization. This latter pool is probably a procaine-sensitive intracellular source of activator Ca mobilized by caffeine and carbachol. The failure of procaine to prevent the response to endothelin in high K, Ca-free medium raises the possibility that this peptide mobilizes an intracellular source of activator Ca, distinct from the caffeine-and carbachol-sensitive pool.

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Section: Effect Of Nifedipinesupporting

confidence: 80%

Section: Generalmentioning

confidence: 99%

mentioning

confidence: 99%

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confidence: 99%

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Multiple sources of calcium for contraction of the human urinary bladder muscle

Maggi

Giuliani

Patacchini

et al. 1989

British J Pharmacology

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“…In the human, rabbit or rat bladder detrusor muscle, the ET-1-induced contractions are slow in developing maximal effect (Maggi et al, 1989a;1990;Lecci et al, 1991) and are sustained. The present results show that both the ET-1-induced rise in bladder tension and the potentiation of the ATP responses, develop maximally within minutes; however, the potentiation of ATP is extraordinarily persistent, much more so than the ET-l-induced contractions.…”

Section: Discussionmentioning

confidence: 99%

Involvement of ET_A receptors in the facilitation by endothelin‐1 of non‐adrenergic non‐cholinergic transmission in the rat urinary bladder

Donoso

Salas

Sepulveda

et al. 1994

British J Pharmacology

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1 Endothelin-1 (ET-1; 3-10 nM) raised the tone of rat bladders bathed in buffer containing atropine (1 gtM) plus guanethidine (3.4 JAM). In addition, ET-1 potentiated, in a concentration-dependent fashion (1-10 nM), 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 (3 nM). 3 The ET-1-induced increase in basal tension reached its maximal effect within 60-90 s. In contrast, the 7.8 JAM ATP-induced contractions increased by 50% within the first minute following incubation with 1O nM ET-1 but required about 5 min to develop the maximal effect. 4 The ET-1-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 3 nM ET-1, recovery required 30 min; applications of 10 nM ET-1 required at least 60 min for full recovery. 5The 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 F2, 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 100 M. Sarafotoxin S6b was 2 to 3 fold less potent than ET-1 whereas sarafotoxin S6c (100 nM) was inactive. AGETB-9 and AGETB-89, two ETB receptor agonists, were also inactive (up to 100 nM). 7 Removal of one or both disulphide bonds in ET-1 and tryptophan-21 formylation of ET-1, resulted in inactive peptides (up to 100 nM). 8 The ET-1 receptor antagonists, BE-18257B and FR 139317, blocked both the ET-1-induced rise in tone and the potentiation of ATP responses in a concentration-dependent fashion. FR 139317 was at least 30 fold more potent than BE-18257B. Both antagonists blocked at lower concentrations the ET-l increase in bladder tone as compared to the ATP potentiation. The antagonism was slowly reversible. 9 Results are consistent with the presence of ETA 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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