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      Muscarinic Receptors Types 1 and 2 in the Preoptic-Anterior Hypothalamic Areas Regulate Ovulation Unequally in the Rat Oestrous Cycle

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          Abstract

          Muscarinic receptors types 1 (m 1AChR) and 2 (m 2AChR) in the preoptic and anterior hypothalamus areas (POA-AHA) were counted, and the effects of blocking these receptors on spontaneous ovulation were analysed throughout the rat oestrous cycle. Rats in each phase of the oestrous cycle were assigned to the following experiments: (1) an immunohistochemical study of the number of cells expressing m 1AChR or m 2AChR in the POA-AHA and (2) analysis of the effects of the unilateral blockade of the m 1AChR (pirenzepine, PZP) or m 2AChR (methoctramine, MTC) on either side of the POA-AHA on the ovulation rate. The number of m 2AChR-immunoreactive cells was significantly higher at 09:00 h on each day of the oestrous cycle in the POA-AHA region, while no changes in the expression profile of m 1AChR protein were observed. The ovulation rate in rats treated with PZP on the oestrous day was lower than that in the vehicle group. Animals treated on dioestrous-1 with PZP or MTC had a higher ovulation rate than those in the vehicle group. In contrast, on dioestrous-2, the MTC treatment decreased the ovulation rate. These results suggest that m 1AChR or m 2AChR in the POA-AHA could participate in the regulation of spontaneous ovulation in rats.

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          Most cited references33

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          Molecular biology of muscarinic acetylcholine receptors.

          Following the molecular cloning of five distinct muscarinic acetylcholine receptor (mAChR) genes, the last decade has witnessed an explosion of new knowledge about how mAChRs function at a molecular level. These studies have been greatly facilitated by the molecular characterization of the many components of the signal transduction pathways activated upon mAChR stimulation. Molecular genetic and biochemical approaches have considerably advanced our knowledge about how mAChRs are assembled, how they bind ligands, and which structural elements on the mAChRs are critical for G protein coupling. In addition, the molecular mechanisms involved in the regulation of mAChR activity (including mAChR sequestration, down-regulation, and phosphorylation) have been explored in great detail. Since the mAChRs are typical members of the superfamily of G protein-coupled receptors, the information gathered with this class of receptors should be of broad general relevance.
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            Characterization of central inhibitory muscarinic autoreceptors by the use of muscarinic acetylcholine receptor knock-out mice.

            Forebrain muscarinic acetylcholine (ACh) receptors (mAChRs; M1-M5) are predicted to play important roles in many fundamental central functions, including higher cognitive processes and modulation of extrapyramidal motor activity. Synaptic ACh levels are known to be regulated by the activity of presynaptic muscarinic autoreceptors mediating inhibition of ACh release. Primarily because of the use of ligands with limited receptor subtype selectivity, classical pharmacological studies have led to conflicting results regarding the identity of the mAChR subtypes mediating this activity in different areas of the brain. To investigate the molecular identity of hippocampal, cortical, and striatal inhibitory muscarinic autoreceptors in a more direct manner, we used genetically altered mice lacking functional M2 and/or M4 mAChRs [knock-out (KO) mice]. After labeling of cellular ACh pools with [3H]choline, potassium-stimulated [3H]ACh release was measured in superfused brain slices, either in the absence or the presence of muscarinic drugs. The nonsubtype-selective muscarinic agonist, oxotremorine (0.1-10 microm), inhibited potassium-stimulated [3H]ACh release in hippocampal, cortical, and striatal slices prepared from wild-type mice by up to 80%. This activity was totally abolished in tissues prepared from M2-M4 receptor double KO mice. Strikingly, release studies with brain slices from M2 and M4 receptor single KO mice indicated that autoinhibition of ACh release is mediated primarily by the M2 receptor in hippocampus and cerebral cortex, but predominantly by the M4 receptor in the striatum. These results, together with additional receptor localization studies, support the novel concept that autoinhibition of ACh release involves different mAChRs in different regions of the brain.
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              A neurogenic timing factor in control of the ovulatory discharge of luteinizing hormone in the cyclic rat.

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                Author and article information

                Journal
                Int J Endocrinol
                Int J Endocrinol
                IJE
                International Journal of Endocrinology
                Hindawi
                1687-8337
                1687-8345
                2017
                14 March 2017
                : 2017
                : 4357080
                Affiliations
                1Laboratory of Neuroendocrinology, Biology of Reproduction Research Unit, Facultad de Estudios Superiores Zaragoza, UNAM, Mexico City, Mexico
                2Department of Basic Research, National Institute of Geriatrics, Mexico City, Mexico
                3Division of Endocrinology, Department of Medicine, Albert Einstein College of Medicine, Bronx, New York City, NY, USA
                Author notes
                *María Esther Cruz: mecbloy@ 123456yahoo.com.mx

                Academic Editor: Michael Horowitz

                Author information
                http://orcid.org/0000-0002-7745-9085
                Article
                10.1155/2017/4357080
                5370522
                486bbc09-0c13-4e66-9b5d-b8319ce123ce
                Copyright © 2017 Yadira L. López-Ramírez et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 20 November 2016
                : 6 February 2017
                Funding
                Funded by: UNAM-DGAPA-PAPIIT
                Award ID: 220014-3
                Categories
                Research Article

                Endocrinology & Diabetes
                Endocrinology & Diabetes

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