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Low Molecular Weight mRNA Encodes a Protein That Controls Serotonin 5-HT_(1c) and Acetylcholine M_1 Receptor Sensitivity in Xenopus Oocytes

Walter, A. E. and Hoger, J. H. and Labarca, C. and Yu, L. and Davidson, N. and Lester, H. A. (1991) Low Molecular Weight mRNA Encodes a Protein That Controls Serotonin 5-HT_(1c) and Acetylcholine M_1 Receptor Sensitivity in Xenopus Oocytes. Journal of General Physiology, 98 (2). pp. 399-417. ISSN 0022-1295. PMCID PMC2229050. doi:10.1085/jgp.98.2.399.

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Serotonin 5-HT_(1c) and acetylcholine M_1 receptors activate phosphoinositidase, resulting in an increased formation of IP_3 and 1,2 diacylglycerol. In Xenopus oocytes injected with mRNA encoding either of these receptors, Ca^(2+) released from intracellular stores in response to IP3 then opens Ca^(2+)-gated Cl^-channels. In the present experiments, oocytes expressing a transcript from a cloned mouse serotonin 5-HT_(1c) receptor were exposed to identical 15-s pulses of agonist, administered 2 min apart; the second current response was two to three times that of the first. However, in those oocytes coinjected with the 5-HT_(1c) receptor transcript and a low molecular weight fraction (0.3-1.5 kb) of rat brain mRNA, the second current response was ~50% of the first. Thus, the low molecular weight RNA encodes a protein (or proteins) that causes desensitization. Experiments using fura-2 or a Ca^(2+)-free superfusate indicated that desensitization of the 5-HT_(1c) receptor response does not result from a sustained elevation of intracellular Ca^(2+) level or require the entry of extracellular Ca^(2+). Photolysis of caged IP_3 demonstrated that an increase in IP_3 and a subsequent rise in Ca^(2+) do not produce desensitization of either the IP_3 or 5-HT_(1c) peak current responses. Furthermore, in oocytes coinjected with the low molecular weight RNA and a transcript from the rat M_1 acetylcholine receptor, the M_1 current response was greatly attenuated. Our data suggest that the proteins involved in attenuation of the M_1 current response and desensitization of the 5-HT_(1c) current response may be the same.

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Lester, H. A.0000-0002-5470-5255
Additional Information:© 1991 Rockefeller University Press. Original version received 9 October 1990 and accepted version received 2January 1991. We thank Dr. Tom I. Bonner for the rat M_1 receptor clone, Dr. N. Gautam for the Gγ clones, and Annie Gouin and Euk Kwon for isolating the oocytes. This work was supported by fellowships from the American Heart Association to A. E. Walter and from the NIH and American Cancer Society to J. H. Hoger, and by grants from the NIH (NS-11756, GM-10991) and The Markey Trust.
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American Heart AssociationUNSPECIFIED
American Cancer SocietyUNSPECIFIED
Lucille P. Markey Charitable TrustUNSPECIFIED
Issue or Number:2
PubMed Central ID:PMC2229050
Record Number:CaltechAUTHORS:20120420-071637268
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Official Citation:Low molecular weight mRNA encodes a protein that controls serotonin 5-HT1c and acetylcholine M1 receptor sensitivity in Xenopus oocytes. A E Walter, J H Hoger, C Labarca, L Yu, N Davidson, and H A Lester J Gen Physiol 1991 98:399-417. Published August 1, 1991, doi:10.1085/jgp.98.2.399
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:30212
Deposited By: Ruth Sustaita
Deposited On:20 Apr 2012 14:42
Last Modified:09 Nov 2021 19:42

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