Nitrergic and purinergic mechanisms and their interactions for relaxation of the rat internal anal sphincter.
1. The NANC neuronal mechanisms for relaxations of the rat internal anal sphincter in response to electrical field stimulation (EFS) were studied in isolated preparations in the presence of atropine (1 microM), propranolol (3 microM) and phentolamine (3 microM). 2. EFS-induced relaxations were abolished by tetrodotoxin (1 microM) and reduced to 64% of control by the guanylate cyclase inhibitor ODQ (1 microM), but were not significantly reduced by the nitric oxide synthase inhibitor L-NAME (100 microM) or oxyhaemoglobin (10 microM). However, in the presence of tubocurarine (10 microM) or apamin (0.1 microM), L-NAME or oxyhaemoglobin greatly reduced or abolished EFS-induced relaxations. 3. The EFS-induced relaxations were mimicked by NO (10-100 microM) and by ATP (3-10 mM). The relaxations elicited by these agents were not affected by tetrodotoxin, L-NAME, tubocurarine or apamin. However, ATP-induced relaxations were reduced by the combination of L-NAME with tubocurarine or apamin. 4. Nicotine (10-100 microM) produced concentration-dependent relaxations that were abolished by tubocurarine (10 microM) or hexamethonium (200 microM). After desensitisation to nicotine (100 microM) and in its continued presence, the addition of L-NAME (100 microM) resulted in almost complete abolition of EFS-induced relaxations. 5. It is suggested that tubocurarine, hexamethonium and desensitisation to nicotine have an apamin-like action in the rat internal anal sphincter, the main effect being blockade of a purinergic component of the relaxant transmission process. 6. The findings suggest that both nitrergic and purinergic transmissions are involved in EFS-induced NANC relaxations of the rat internal anal sphincter, and there appears to be a complex interaction between these two pathways of transmission.
De Luca
A
A
Department of Medical Laboratory Science, Royal Melbourne Institute of Technology University, Victoria, Australia.
Li
C G
CG
Rand
M J
MJ
D018674:Adrenergic Antagonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D001003:Anal Canal / Q000187:drug effects*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D004347:Drug Interactions; D004558:Electric Stimulation; D066298:In Vitro Techniques; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D009569:Nitric Oxide / Q000494:pharmacology*; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats
D018674:Adrenergic Antagonists; D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D009569:Nitric Oxide; D001285:Atropine; D011433:Propranolol; D010646:Phentolamine