ROLE OF Ca-ACTIVATED K CHANNELS AND Na,K-ATPase IN PROSTAGLANDIN E- AND E-INDUCED INHIBITION OF THE ADRENERGIC RESPONSE IN HUMAN VAS DEFERENS

Pascual Medina (1) , Gloria Segarra (1) , María Dolores Mauricio (1) , José M. Vila (1) , Pascual Chuan (2) , Salvador Lluch (1)

1 Facultad de Medicina y Odontología
2 Servicio de Urología Hospital Clínico Universitario

We studied the role of K channels and Na,K-ATPase in the presynaptic inhibitory effects of prostaglandin E (PGE) and PGE on the adrenergic responses of human vas deferens. Furthermore, we determined the effects of increasing extracellular K concentrations ([K]) and inhibition of Na,K-ATPase on neurogenic and norepinephrine -induced contractile responses. Ring segments of the epididymal part of the vas deferens were taken from 45 elective vasectomies and mounted in organ baths for isometric recording of tension. The neuromodulatory effects of PGEs were tested in the presence of K channel blockers. PGE and PGE (10 - 10 M) induced inhibition of adrenergic contractions. The presence of tetraethylammonium (10 M), charybdotoxin (10 M), or iberiotoxin (10 M), prevented the inhibitory effects of PGE and PGE on the adrenergic contraction. Both glibenclamide (10 M) and apamin (10 M) failed to antagonize PGE and PGE effects. Raising the [K] from 15.8mM to 25.8mM caused inhibition of the neurogenic contractions. Ouabain at a concentration insufficient to alter the resting tension (10 M) increased contractions induced by electrical stimulation but did not alter the contractions to norepinephrine. The inhibition of neurogenic responses induced PGE, PGE and increased extracellular concentration of K was almost completely prevented by ouabain (10 M). The results demonstrate that PGE and PGE inhibit adrenergic responses by a prejunctional mechanism that involves the activation of large-conductance Ca-activated K channels and Na,K-ATPase.

Mots clés: Electrical field stimulation; Human vas deferens; Norepinephrine; Potassium channels; Prostaglandins; Smooth muscle; Smooth muscle.

Domaines: Pharmacologie

Pascual Medina, Gloria Segarra, María Dolores Mauricio, José M. Vila, Pascual Chuan, et al.. ROLE OF Ca-ACTIVATED K CHANNELS AND Na,K-ATPase IN PROSTAGLANDIN E- AND E-INDUCED INHIBITION OF THE ADRENERGIC RESPONSE IN HUMAN VAS DEFERENS. Biochemical Pharmacology, 2011, 82 (1), pp.65. ⟨10.1016/j.bcp.2011.03.021⟩. ⟨hal-00701260⟩