Effects of beta-adrenoceptor antagonists in the neural nitric oxide release induced by electrical field stimulation and sodium channel activators in the rabbit corpus cavernosum.
Beta-Adrenoceptor antagonists may present receptor-independent mechanisms, such as blockade of voltage-gated sodium channels. This study aimed to investigate the effects of non-selective (propranolol), and selective beta1- (atenolol, metoprolol and betaxolol) and beta2-adrenoceptor (ICI 118,551) antagonists in the nitric oxide (NO)-mediated rabbit corpus cavernosum relaxations induced by either electrical field stimulation (EFS) or activators of voltage-gated sodium channels. The sodium channel blockers tetrodotoxin and saxitoxin abolished the relaxations induced by EFS or sodium channel activators of binding site-2 (aconitine and veratridine), site-3 (Ts3 toxin), site-4 (Ts1 toxin) and site-5 (brevetoxin-3). The beta-adrenoceptor antagonists failed to affect the relaxations induced by EFS, aconitine and veratridine. Relaxations induced by Ts3 and Ts1 toxins, as well as brevetoxin-3, were markedly reduced by prior addition of propranolol, betaxolol and ICI 118,551. During the established relaxation induced by Ts3 toxin, propranolol failed to restore the basal tone. In conclusion, beta-adrenoceptor antagonists may cause an allosteric inhibition at the binding site-3, -4 and -5 of voltage-gated sodium channels, leading to blockade of neural NO release.
Teixeira
Cleber E
CE
Department of Pharmacology, Faculty of Medical Sciences, UNICAMP, P.O. Box 6111, 13081-970, Campinas (SP), Brazil.
Baracat
Juliana S
JS
Arantes
Eliane C
EC
De Nucci
Gilberto
G
Antunes
Edson
E
D000157:Aconitine / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D015784:Betaxolol / Q000494:pharmacology; D001665:Binding Sites; D004558:Electric Stimulation; D066298:In Vitro Techniques; D019476:Insect Proteins; D008297:Male; D008790:Metoprolol / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects; D009498:Neurotoxins / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D010413:Penis / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D011412:Propanolamines / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011817:Rabbits; D012530:Saxitoxin / Q000494:pharmacology; D012604:Scorpion Venoms / Q000494:pharmacology; D062687:Sodium Channel Agonists; D013779:Tetrodotoxin / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D019476:Insect Proteins; D009498:Neurotoxins; D011412:Propanolamines; D012604:Scorpion Venoms; D062687:Sodium Channel Agonists; C120263:scorpion toxin Ts1, Tityus; D009569:Nitric Oxide; D012530:Saxitoxin; D013779:Tetrodotoxin; C026777:ICI 118551; D001262:Atenolol; D014701:Veratridine; D011433:Propranolol; D008790:Metoprolol; D015784:Betaxolol; D000157:Aconitine