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  • Title: Cryptolepine-induced vasodilation in the isolated perfused kidney of the rat: role of G-proteins, K+ and Ca2+ channels.
    Author: Oyekan AO.
    Journal: Eur J Pharmacol; 1995 Oct 04; 285(1):1-9. PubMed ID: 8846804.
    Abstract:
    The isolated perfused kidney of the rat was used to examine the contribution by guanosine triphosphate (GTP)-binding (G-) proteins, K+ and Ca2+ channels to the vasodilator actions of cryptolepine (5-methylquindoline). In normal Krebs-Henseleit buffer (4.7 mM KCl), cryptolepine elicited dose-dependent reductions in perfusion pressure of phenylephrine-preconstricted kidneys. The reductions in perfusion pressure by cryptolepine at bolus doses of 2.5, 5, and 10 micrograms were -18.0 +/- 3.4, -30.6 +/- 5.3, and -38.3 +/- 6.8 mm Hg, respectively (n = 19). In K(+)-free (0 mM KCl) Krebs-Henseleit solution, the vasodilator response to cryptolepine was reduced by 44.7 +/- 5.7% (n = 5; P < 0.01). The addition of ouabain (10(-4) M) further reduced cryptolepine-induced vasodilation to 63.0 +/- 7.2% (n = 11: P < 0.01) of the control. A combination of both conditions did not abolish the vasodilator responses to cryptolepine, suggesting the involvement of additional mechanisms. In 80, as opposed to 20 mM KCl, the reductions in perfusion pressure by cryptolepine, 2.5, 5, and 10 micrograms were markedly reduced to -0.8 +/- 0.8, -2.3 +/- 1.4, and -4.0 +/- 2.1 mm Hg, respectively (P < 0.01; n = 6). Responses to acetylcholine and diazoxide, an adenosine triphosphate (ATP)-dependent K+ channel activator, were also markedly reduced, suggesting the involvement of K+ channels for these agents. Furthermore, tetraethylammonium (5 and 10 mM), a non-specific K+ channel blocker, inhibited the vasodilator responses to cryptolepine (n = 5; P < 0.01) and to diazoxide and acetylcholine in a dose-related manner. However, glibenclamide (5 and 10 microM), an ATP-sensitive K+ channel blocker, inhibited the vasodilator responses to diazoxide and acetylcholine but was without effect on cryptolepine-induced vasodilation. This suggests that cryptolepine activates K+ channels which are tetraethyl ammonium- but not glibenclamide-sensitive. In pertussis toxin-treated rats, the vasodilator response to cryptolepine was not affected while that to acetylcholine and especially diazoxide was markedly inhibited. This suggests that, unlike diazoxide and acetylcholine, the K+ channels activated by cryptolepine are not coupled to pertussis toxin-sensitive G-proteins. In the presence of verapamil (5 microM) and cobalt chloride (1 mM), Ca2+ channel blockers, the vasodilator response to cryptolepine was inhibited (n = 5; P < 0.01), suggesting that Ca2+ flux across membranes is also involved in cryptolepine-induced vasodilation in the rat kidney.
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