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Electrical field stimulation inhibits the contractile response to noradrenaline of the rat external urethral sphincter
380
Pharmacological Research. Vol. 22. Supplement 2.1990
ELECTRICAL FIELD STIMULATION INHIBITS THE CONTRACTILE RESPONSE TO NORADRENALINE OF THE RAT EXTERNAL URETHRAL SPHINCTER. !:iillillJl...M, Maggi CN, Lopez G, Giachetti A* and Conte B. Pharmacology Dept., Menarini Ricerche Sud, Pomezia (Rome) 'Pharmacology Dept., Menarini Pharmaceuticals, Firenze. 1) Electrical Field Stimulation (EFS) (2.5 Hz, 60 V, 1 ms, trains of 5 severy 5 min) of the rat isolated external urethral sphincter (EUS) at rest (1) produced a contractile response characterized by two components: a "slow" tonic contraction on which was superimposed a series of phasic "twitch-like" contractions. As elsewhere described (2), both components were tetrodotoxin (TTX) -sensitive while the twitches were also D-tubocurarine (D-Tc) -sensitive. 2) Administration of noradrenaline (0.1mM) produced a biphasic contraction of the preparations: an initial rapid contraction (240±19 mg), followed by a well mantained tonus lasting 20-30 min. .3) This response was completely inhibited by previous administration of phentolamine (2.6 IlM) while it was unaffected by exposure to TTX (0.6 ~lM). 4} EFS performed when the noradrenaline-induced urethral contraction had reached a steady state (15 min), still produced a biphasic response: a marked relaxation (87±9.6 rng), on which were superimposed the fast twitch-like D-Tc -senslnve contractions. 5) EFS-induced relaxation has neurogenic orrqm since is abolished by administration of TTX (0.6 IlM). Conversely, propranolol (3 Il~) or atropine (~~uM) did not affect the relaxation. S) EFS did not produce relaxation of the noradrenaline-induced urethral contraction in rats, pudendal nerves of which were bilaterally sectioned 10 days before. while EFS-induced relaxation was reduced by about 30% when the major pelvic ganglia have been chronically removed. 7) Altoghether these findings indicate that non-adrenergic, non-cholinergic fibers travelling in the pudendal nerves innervate the smooth portion of the EUS in rats, like in other species (3), and play an inhibitory role. Experiments are in progress to extablish the rnediator/s involved in this inhibition.
1) WatanRbe H et al: J. Anal. (1979) 128,4 2) Conte B et al : 2 c Convegno Naz. Societa It. Neuroscienze (1989) 3) Mattiasson A et al: J. Urol. (1985 )133, 298
1043--6618/90/22110380-0 I/$03.00/0
© 1990 The Italian Pharmacological Society
Pharmacological Research. Vol. 22. Supplement 2.1990
ELECTRICAL FIELD STIMULATION INHIBITS THE CONTRACTILE RESPONSE TO NORADRENALINE OF THE RAT EXTERNAL URETHRAL SPHINCTER. !:iillillJl...M, Maggi CN, Lopez G, Giachetti A* and Conte B. Pharmacology Dept., Menarini Ricerche Sud, Pomezia (Rome) 'Pharmacology Dept., Menarini Pharmaceuticals, Firenze. 1) Electrical Field Stimulation (EFS) (2.5 Hz, 60 V, 1 ms, trains of 5 severy 5 min) of the rat isolated external urethral sphincter (EUS) at rest (1) produced a contractile response characterized by two components: a "slow" tonic contraction on which was superimposed a series of phasic "twitch-like" contractions. As elsewhere described (2), both components were tetrodotoxin (TTX) -sensitive while the twitches were also D-tubocurarine (D-Tc) -sensitive. 2) Administration of noradrenaline (0.1mM) produced a biphasic contraction of the preparations: an initial rapid contraction (240±19 mg), followed by a well mantained tonus lasting 20-30 min. .3) This response was completely inhibited by previous administration of phentolamine (2.6 IlM) while it was unaffected by exposure to TTX (0.6 ~lM). 4} EFS performed when the noradrenaline-induced urethral contraction had reached a steady state (15 min), still produced a biphasic response: a marked relaxation (87±9.6 rng), on which were superimposed the fast twitch-like D-Tc -senslnve contractions. 5) EFS-induced relaxation has neurogenic orrqm since is abolished by administration of TTX (0.6 IlM). Conversely, propranolol (3 Il~) or atropine (~~uM) did not affect the relaxation. S) EFS did not produce relaxation of the noradrenaline-induced urethral contraction in rats, pudendal nerves of which were bilaterally sectioned 10 days before. while EFS-induced relaxation was reduced by about 30% when the major pelvic ganglia have been chronically removed. 7) Altoghether these findings indicate that non-adrenergic, non-cholinergic fibers travelling in the pudendal nerves innervate the smooth portion of the EUS in rats, like in other species (3), and play an inhibitory role. Experiments are in progress to extablish the rnediator/s involved in this inhibition.
1) WatanRbe H et al: J. Anal. (1979) 128,4 2) Conte B et al : 2 c Convegno Naz. Societa It. Neuroscienze (1989) 3) Mattiasson A et al: J. Urol. (1985 )133, 298
1043--6618/90/22110380-0 I/$03.00/0
© 1990 The Italian Pharmacological Society