The motor response to ethylenediamine of the rat isolated duodenum: involvement of GABAergic transmission?
We have studied the motor response to ethylenediamine (EDA), a well known releaser of endogenous GABA, on the longitudinal muscle of the rat isolated proximal duodenum in presence of atropine (3 microM) and guanethidine (3 microM). EDA produced a concentration-(0.03-3 microM)-dependent relaxation which was potentiated when the preparations were exposed to GABA during the equilibration period. The GABA-induced potentiation of the response to EDA was prevented by nipecotic acid, an inhibitor of GABA uptake. The response to EDA was partially inhibited by 3-mercaptopropionic acid, a known inhibitor of GABA release. However, contrary to the relaxant response produced by exogenous GABA, the EDA-induced relaxation was picrotoxin-(0.1 microM)-resistant. In preparations pre-exposed to GABA, the response to EDA was partially tetrodotoxin-(1 microM)-sensitive. By contrast, in preparations not exposed to GABA, the EDA-induced relaxation was totally tetrodotoxin resistant. The response to EDA was abolished or largely inhibited in preparations excised from rats in which the proximal duodenum was chemically denervated by exposure (2 weeks before), to benzalkonium chloride (BZK). Likewise, the indirect relaxations produced by electrical field simulation. DMPP, capsaicin or GABA were abolished by BZK pretreatment while noradrenaline was still effective. These findings indicate that the relaxant response to EDA is neurogenic in origin, while being largely tetrodotoxin-resistant. A GABAergic mechanism could be involved but also other inhibitory transmitter(s) should be taken into account. EDA appears a useful tool to study the inhibitory non-adrenergic non-cholinergic innervation of the rat proximal duodenum.
Maggi
C A
CA
Pharmacology Department, Research Laboratories, A. Menarini Pharmaceuticals, Florence, Italy.
Giuliani
S
S
Santicioli
P
P
Selleri
S
S
Meli
A
A
D015097:3-Mercaptopropionic Acid / Q000494:pharmacology; D000818:Animals; D001548:Benzalkonium Compounds / Q000494:pharmacology; D004386:Duodenum / Q000187:drug effects; D005029:Ethylenediamines / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009557:Nipecotic Acids / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology; D011392:Proline / Q000031:analogs & derivatives*; D051381:Rats; D011919:Rats, Inbred Strains; D009435:Synaptic Transmission / Q000187:drug effects*; D013779:Tetrodotoxin / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D015097:3-Mercaptopropionic Acid; D001548:Benzalkonium Compounds; D005029:Ethylenediamines; D009557:Nipecotic Acids; D010852:Picrotoxin; D011392:Proline; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; C030278:nipecotic acid; C031234:ethylenediamine; C010983:homoproline