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Pituitary-adrenal responses to oxotremorine and acute stress in male and female M1 muscarinic receptor knockout mice: comparisons to M2 muscarinic receptor knockout mice.
J Neuroendocrinol. 2008 May; 20(5):617-25.JN

Abstract

Both within the brain and in the periphery, M(1) muscarinic receptors function primarily as postsynaptic receptors and M(2) muscarinic receptors function primarily as presynaptic autoreceptors. In addition to classical parasympathetic effectors, cholinergic stimulation of central muscarinic receptors influences the release of adrenocorticotrophic hormone (ACTH) and corticosterone. We previously reported that oxotremorine administration to male and female M(2) receptor knockout and wild-type mice increased ACTH to a significantly greater degree in knockout males compared to all other groups, and that M(2) knockout mice of both sexes were significantly more responsive to the mild stress of saline injection than were wild-type mice. These results accord with the primary function of M(2) receptors as presynaptic autoreceptors. In the present study, we explored the role of the M(1) receptor in pituitary-adrenal responses to oxotremorine and saline in male and female M(1) knockout and wild-type mice. Because these mice responded differently to the mild stress of saline injection than did the M(2) knockout and wild-type mice, we also determined hormone responses to restraint stress in both M(1) and M(2) knockout and wild-type mice. Male and female M(1) knockout and wild-type mice were equally unresponsive to the stress of saline injection. Oxotremorine increased both ACTH and corticosterone in M(1) wild-type mice to a significantly greater degree than in knockout mice. In both M(1) knockout and wild-type animals, ACTH responses were greater in males compared to females, and corticosterone responses were greater in females compared to males. Hormone responses to restraint stress were increased in M(2) knockout mice and decreased in M(1) knockout mice compared to their wild-type counterparts. These findings suggest that M(1) and M(2) muscarinic receptor subtypes differentially influence male and female pituitary-adrenal responses to cholinergic stimulation and stress. The decreased pituitary-adrenal sensitivity to oxotremorine and restraint stress noted in M(1) knockout mice is consistent with M(1) being primarily a postsynaptic receptor. Conversely, the increased pituitary-adrenal sensitivity to these challenges noted in M(2) knockout mice is consistent with M(2) being primarily a presynaptic autoreceptor.

Authors+Show Affiliations

Department of Biology, Saint Vincent College, Latrobe, PA 15650-2690, USA. michael.rhodes@email.stvincent.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

18363805

Citation

Rhodes, M E., et al. "Pituitary-adrenal Responses to Oxotremorine and Acute Stress in Male and Female M1 Muscarinic Receptor Knockout Mice: Comparisons to M2 Muscarinic Receptor Knockout Mice." Journal of Neuroendocrinology, vol. 20, no. 5, 2008, pp. 617-25.
Rhodes ME, Rubin RT, McKlveen JM, et al. Pituitary-adrenal responses to oxotremorine and acute stress in male and female M1 muscarinic receptor knockout mice: comparisons to M2 muscarinic receptor knockout mice. J Neuroendocrinol. 2008;20(5):617-25.
Rhodes, M. E., Rubin, R. T., McKlveen, J. M., Karwoski, T. E., Fulton, B. A., & Czambel, R. K. (2008). Pituitary-adrenal responses to oxotremorine and acute stress in male and female M1 muscarinic receptor knockout mice: comparisons to M2 muscarinic receptor knockout mice. Journal of Neuroendocrinology, 20(5), 617-25. https://doi.org/10.1111/j.1365-2826.2008.01700.x
Rhodes ME, et al. Pituitary-adrenal Responses to Oxotremorine and Acute Stress in Male and Female M1 Muscarinic Receptor Knockout Mice: Comparisons to M2 Muscarinic Receptor Knockout Mice. J Neuroendocrinol. 2008;20(5):617-25. PubMed PMID: 18363805.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pituitary-adrenal responses to oxotremorine and acute stress in male and female M1 muscarinic receptor knockout mice: comparisons to M2 muscarinic receptor knockout mice. AU - Rhodes,M E, AU - Rubin,R T, AU - McKlveen,J M, AU - Karwoski,T E, AU - Fulton,B A, AU - Czambel,R K, Y1 - 2008/03/15/ PY - 2008/3/28/pubmed PY - 2008/7/4/medline PY - 2008/3/28/entrez SP - 617 EP - 25 JF - Journal of neuroendocrinology JO - J Neuroendocrinol VL - 20 IS - 5 N2 - Both within the brain and in the periphery, M(1) muscarinic receptors function primarily as postsynaptic receptors and M(2) muscarinic receptors function primarily as presynaptic autoreceptors. In addition to classical parasympathetic effectors, cholinergic stimulation of central muscarinic receptors influences the release of adrenocorticotrophic hormone (ACTH) and corticosterone. We previously reported that oxotremorine administration to male and female M(2) receptor knockout and wild-type mice increased ACTH to a significantly greater degree in knockout males compared to all other groups, and that M(2) knockout mice of both sexes were significantly more responsive to the mild stress of saline injection than were wild-type mice. These results accord with the primary function of M(2) receptors as presynaptic autoreceptors. In the present study, we explored the role of the M(1) receptor in pituitary-adrenal responses to oxotremorine and saline in male and female M(1) knockout and wild-type mice. Because these mice responded differently to the mild stress of saline injection than did the M(2) knockout and wild-type mice, we also determined hormone responses to restraint stress in both M(1) and M(2) knockout and wild-type mice. Male and female M(1) knockout and wild-type mice were equally unresponsive to the stress of saline injection. Oxotremorine increased both ACTH and corticosterone in M(1) wild-type mice to a significantly greater degree than in knockout mice. In both M(1) knockout and wild-type animals, ACTH responses were greater in males compared to females, and corticosterone responses were greater in females compared to males. Hormone responses to restraint stress were increased in M(2) knockout mice and decreased in M(1) knockout mice compared to their wild-type counterparts. These findings suggest that M(1) and M(2) muscarinic receptor subtypes differentially influence male and female pituitary-adrenal responses to cholinergic stimulation and stress. The decreased pituitary-adrenal sensitivity to oxotremorine and restraint stress noted in M(1) knockout mice is consistent with M(1) being primarily a postsynaptic receptor. Conversely, the increased pituitary-adrenal sensitivity to these challenges noted in M(2) knockout mice is consistent with M(2) being primarily a presynaptic autoreceptor. SN - 1365-2826 UR - https://www.unboundmedicine.com/medline/citation/18363805/Pituitary_adrenal_responses_to_oxotremorine_and_acute_stress_in_male_and_female_M1_muscarinic_receptor_knockout_mice:_comparisons_to_M2_muscarinic_receptor_knockout_mice_ DB - PRIME DP - Unbound Medicine ER -