Characterization of the non‐nitrergic NANC relaxation responses in the rabbit vaginal wall

• Published in: British journal of pharmacology Vol. 135; no. 2; pp. 546 - 554
• Main Authors: Ziessen, Tom, Moncada, Salvador, Cellek, Selim
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.01.2002; Nature Publishing
• Subjects: Adrenergic Fibers - drug effects; Adrenergic Fibers - physiology; Animals; Biological and medical sciences; Cholinergic Fibers - drug effects; Cholinergic Fibers - physiology; Chymotrypsin - pharmacology; Electric Stimulation; Enzyme Inhibitors - pharmacology; Female; Fundamental and applied biological sciences. Psychology; Hormone metabolism and regulation; In Vitro Techniques; Mammalian female genital system; Muscle Relaxation - drug effects; Muscle Relaxation - physiology; Neuropeptides - pharmacology; Neuropeptides - physiology; Nitrergic Neurons - drug effects; Nitrergic Neurons - physiology; Nitric oxide; Nitric Oxide Synthase - antagonists & inhibitors; Nitric Oxide Synthase - metabolism; Nitric Oxide Synthase Type I; non‐adrenergic; non‐cholinergic; Oxadiazoles - pharmacology; Perfusion; Quinoxalines - pharmacology; rabbit; Rabbits; Rats; Rats, Sprague-Dawley; vagina; Vagina - drug effects; Vagina - enzymology; Vagina - physiology; vasoactive intestinal peptide; Vertebrates: reproduction; Enzyme; Phosphorus-oxygen lyases; Cyclic AMP; Rabbit; Non adrenergic non cholinergic transmission; Vagina; 3',5'-GMP; Smooth muscle; Lyases; Lagomorpha; Guanylate cyclase; Biological activity; Nitric-oxide synthase; Muscular relaxation; Vertebrata; Regulation(control); Mammalia; Antispasmodic agent; Animal; Female genital system; Vasoactive intestinal peptide; Oxidoreductases; Intracellular; Mechanism of action
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0704481

Electrical field stimulation (EFS)‐induced non‐adrenergic non‐cholinergic (NANC) relaxation responses in the rabbit vaginal wall were investigated. These NANC responses were partially inhibited with the nitric oxide synthase (NOS) inhibitors NG‐nitro‐L‐arginine methyl ester (L‐NAME; 500 μM), NG‐nitro‐L‐arginine (300 μM) or N‐iminoethyl‐L‐ornithine (500 μM) or the selective soluble guanylate cyclase inhibitor 1H‐[1,2,4]oxadiazolo[4,3,‐a]quinoxalin‐1‐one (ODQ, 10 μM). Application of L‐NAME and ODQ concomitantly did not increase the degree of inhibition. L‐NAME or ODQ were observed to be more effective at low frequencies. The resistant part of the responses was more pronounced at higher frequencies and was completely inhibited by tetrodotoxin (1 μM). Exogenous application of the peptides vasoactive intestinal peptide (VIP), pituitary adenylate cyclase activating peptide (PACAP‐27 and PACAP‐38), peptide histidine methionine (PHM), peptide histidine valine (PHV), helospectin‐I or ‐II induced a relaxation response. Calcitonin gene‐related peptide or substance P did not cause any relaxation. The peptidase α‐chymotrypsin (type II; 2 units ml−1) did not affect non‐nitrergic NANC responses, although it did inhibit relaxation responses elicited by exogenous VIP, PACAP‐27, PACAP‐38, PHM, PHV, helospectin‐I or ‐II. K+ channel inhibitors apamin (1 μM) or charybdotoxin (100 nM) when used alone or in conjunction did not affect non‐nitrergic NANC responses. The non‐nitrergic NANC responses were not associated with any increase in intracellular cyclic adenosine‐3′, 5′‐monophosphate (cyclic AMP) or cyclic guanosine‐3′, 5′‐monophosphate (cyclic GMP) concentrations. The peptide‐induced relaxations were all associated with increases in cyclic AMP concentrations. These results suggest that a neuronal factor elicits non‐nitrergic NANC responses in the rabbit vaginal wall. The identity of this factor remains to be established. British Journal of Pharmacology (2002) 135, 546–554; doi:10.1038/sj.bjp.0704481