Cholinergic innervation of the mouse isolated vas deferens

• Published in: British journal of pharmacology Vol. 146; no. 7; pp. 927 - 934
• Main Authors: Cuprian, Alina M, Solanki, Pravesh, Jackson, Margaret V, Cunnane, Thomas C
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.12.2005; Nature Publishing
• Subjects: acetylcholine; Acetylcholine - pharmacology; Animals; Atropine - pharmacology; Biological and medical sciences; bretylium; Bretylium Compounds - pharmacology; contraction studies; Cyclopentolate - pharmacology; Male; Medical sciences; Mice; Mice, Inbred BALB C; Mouse vas deferens; Muscle Contraction - drug effects; neostigmine; Neostigmine - pharmacology; Nicotine - pharmacology; Parasympathetic Nervous System - physiology; Pharmacology. Drug treatments; Prazosin - pharmacology; Vas Deferens - drug effects; Vas Deferens - innervation; Vas Deferens - physiology; Yohimbine - pharmacology; Semen pathway; Rodentia; contraction studies; Male genital duct; Male genital system; Vas deferens; Vertebrata; Mammalia; Mouse vas deferens; Mouse; bretylium; Animal; Neurotransmitter; Cholinergic innervation; Acetylcholine; neostigmine
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0706357

Recently, a population of nerves has been described in the aganglionic mouse vas deferens, in which electrically evoked contractions were insensitive to high concentrations of the adrenergic neurone blocker, bretylium. In this paper, the pharmacology of this nerve‐evoked contraction has been examined in more detail. Bretylium (20 μM) revealed, after 5 h exposure, a new residual neurogenic contraction (20 stimuli at 10 Hz) that was tetrodotoxin‐sensitive. The muscarinic antagonist, cyclopentolate (0.1 and 1 μM), reduced this residual component and the inhibition was reversed by the acetylcholinesterase inhibitor, neostigmine (1 and 10 μM). Nicotine (30 μM) enhanced the residual component revealed by bretylium, suggesting that there are prejunctional nicotinic receptors (nAchRs) influencing acetylcholine (Ach) release. In the presence of prazosin (0.1 μM), a selective α1‐adrenoceptor antagonist, and α,β‐methylene ATP (1 μM), a purinergic agonist that desensitise P2X receptors, neostigmine increased the hump component of contraction and yohimbine (0.3 μM), an α2‐adrenoceptor antagonist, enhanced both components of the electrically evoked stimulation. The contraction was blocked by cyclopentolate (1 μM). In the absence of bretylium, neostigmine alone increased the hump component of contraction in a frequency‐dependent manner. This increase was reversed by atropine (1 μM) and cyclopentolate (1 μM) to control levels. However, in control experiments, atropine or cyclopentolate did not detectably influence the delayed neurogenic contraction. Ach (10 μM) induced a contraction in the mouse vas deferens, either when applied alone or in the presence of neostigmine. Thus, it has been demonstrated unequivocally that the mouse vas deferens is innervated by functional cholinergic nerves, whose action is terminated by cholinesterase. Furthermore, Ach release can be enhanced by activation of prejunctional nAchRs presumably located on the cholinergic nerve terminals. British Journal of Pharmacology (2005) 146, 927–934. doi:10.1038/sj.bjp.0706357