1.Muscarinic receptor antagonism at the spinal cord level causes inhibitory effects on male rat sexual behavior.
Gómez-Martínez LE;Cueva-Rolón R Behav Brain Res. 2009 Nov 5;203(2):247-55. doi: 10.1016/j.bbr.2009.05.010. Epub 2009 May 18.
The role of cholinergic neurotransmission in male rat sexual behavior at the brain level has been studied by several researchers. However, little is known about its role at the spinal cord level. In this study, the effects of the intrathecal (IT) administration of the muscarinic receptor antagonist subtypes (MRAs) methoctramine (Meth), tropicamide (Trop) and 4-DAMP on male rat sexual behavior were evaluated during three ejaculatory series. Meth and Trop are preferring antagonists for the M2/M4 receptor subtypes, and 4-DAMP is a preferring antagonist for the M3 receptor subtype. All the MRAs tested noticeably inhibited male rat copulatory behavior, reflected by a reduction in the number of animals engaging in sexual behavior and a gradual decrease in the number of animals able to ejaculate. Significant increases in intromission latency (IL), ejaculation latency (EL) and post-ejaculatory interval (PEI) were observed. The ranking of inhibitory potency in all recorded parameters was Meth>/=4-DAMP>Trop. In theory, the effects of Meth and Trop could be a result of interaction with M2/M4 receptors. However, given that the M2 receptor constitutes the greatest population of muscarinic receptors at all spinal cord sites and given the high affinity for Meth on M2 receptors, the high potency in the inhibitory effects of Meth is indicative of the special role of M2 spinal receptors in the implementation of this behavior.
2.Sialogogic activities of SNI-2011 compared with those of pilocarpine and McN-A-343 in rat salivary glands: identification of a potential therapeutic agent for treatment of Sjörgen's syndrome.
Iwabuchi Y;Masuhara T Gen Pharmacol. 1994 Jan;25(1):123-9.
1. We examined the sialogogic activities in rat major salivary glands of SNI-2011, in comparison with those of pilocarpine and McN-A-343, and we characterized the subtypes of muscarine receptors that are involved in the sialogogic responses to SNI-2011 and McN-A-343. 2. SNI-2011 at doses ranging from 1 to 10 mg/kg (i.v.) increased the secretion of saliva in a dose-dependent manner. The dose-response curves for SNI-2011 were approximately parallel to curves for pilocarpine but the potency of SNI-2011 was about 25-fold lower than that of pilocarpine. 3. The total volume of saliva secreted in response to McN-A-343 was very much less than that secreted in response to SNI-2011. 4. The salivation induced by SNI-2011 and by McN-A-343 was inhibited by various antagonists with the following rank order of potency: 4-DAMP >> pirenzepine >> AF-DX 116. 5. Our results suggest that the sialogogic effects of SNI-2011 and McN-A-343 are mediated by direct stimulation of M3 receptors in salivary glands and that SNI-2011 may prove useful in the management of xerostomia in patients with Sjögren's syndrome.
3.The interaction of l-cysteine/H
Aydinoglu F;Dalkir FT;Demirbag HO;Ogulener N Nitric Oxide. 2017 Nov 1;70:51-58. doi: 10.1016/j.niox.2017.08.005. Epub 2017 Aug 25.
The aim of this study was to investigate the possible interaction of l-cysteine/H;2;S pathway and muscarinic acetylcholine receptors (mAChRs) in the mouse corpus cavernosum (CC). l-cysteine (endogenous H;2;S substrate; 10;-6;-10;-3; M), sodium hydrogen sulfide (NaHS; exogenous H;2;S; 10;-6;-10;-3; M) and acetylcholine (10;-9;-10;-4; M) produced concentration-dependent relaxation in isolated mouse CC tissues. Relaxations to endogenous and exogenous H;2;S were reduced by non-selective mAChR antagonist atropine (5 × 10;-5; M), selective M;1; mAChR antagonist pirenzepine (5 × 10;-5; M) and selective M;3; mAChR antagonist 4-DAMP (10;-7; M) but not by selective M;2; mAChR antagonist AF-DX 116 (10;-6; M). Also, acetylcholine-induced relaxations were reduced by atropine, pirenzepine, 4-DAMP and AF-DX 116, confirming the selective effects of mAChR antagonists. Furthermore, acetylcholine-induced relaxations were attenuated by cystathionine-gamma-lyase (CSE) inhibitor d,l-propargylglycine (PAG, 10;-2; M) and cystathionine-β-synthase inhibitor (CBS) aminooxyacetic acid (AOAA, 10;-3; M). l-nitroarginine, nitric oxide synthase inhibitor, augmented the inhibitory effects of mAChR antagonists and H;2;S enzyme inhibitors on acetylcholine-induced relaxations.