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

Abstract

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.

Characterization of ibodutant at NK2 receptor in human colon

“…After a further 45 min equilibration period, during which the medium was renewed every 15 min, nifedipine (0.3 mM) was added to the Krebs solution and there was left in all subsequent experimental phases to eliminate spontaneous activity (Maggi et al 1989;Zagorodnyuk et al 1994). After 30 min of incubation in the presence of nifedipine the preparations were challenged with 1 mM [bAla 8 ]NKA(4-10) to evaluate the contractile response of each preparation.…”

Pharmacology of the Lower Urinary Tract: Basis for Current and Future Treatments of Urinary Incontinence

“…The ET-1-induced contractions were not significantly affected by scopolamine or indomethacin, but could be abolished by incubation in a Ca 2ϩ -free solution, and nifedipine had a marked inhibitory action. On the other hand, in human detrusor, the ET-1-induced contractions were resistant to nifedipine (Maggi et al, 1989d), illustrating species variation in the activation mechanisms. In rabbit bladder, Traish et al (1992) found that ET-1, ET-2, and ET-3 all caused concentration-dependent contractions.…”

Characterization of endothelin (ET) receptors in the isolated gall bladder of the guinea‐pig: evidence for an additional ET receptor subtype

“…ET/SX peptides are also potent contractors of non-vascular smooth muscle preparations such as airways (Battistini et al, 1992;Hay et al, 1993), the urinary bladder (Maggi et al, 1989b;Saenz de Tejada et al, 1992;Traish et al, 1992), the uterus (Bousso-Mittler et al, 1989;Svane et al, 1993; Rae et al, 1993), the stomach fundus (Wood et al, 1992;Warner 1993a), the ileum (Maggi et al, 1989a;Wollberg et al, 1991;Guimaraes & Rae, 1992;Miasiro et al, 1993;Warner et al, 1993b), the colon (Lin & Lee, 1990;Takahashi et al, 1990) and the gall bladder (Maggi et al, 1990; Moummi et al, 1992). To date, two distinct ET receptors (ETA and ETB; Sakurai et al, 1992) have been cloned from mammalian species.…”