scholarly journals Differential Actions of Muscarinic Receptor Subtypes in Gastric, Pancreatic, and Colon Cancer

2021 ◽  
Vol 22 (23) ◽  
pp. 13153
Author(s):  
Alyssa Schledwitz ◽  
Margaret H. Sundel ◽  
Madeline Alizadeh ◽  
Shien Hu ◽  
Guofeng Xie ◽  
...  
Keyword(s):  
Muscarinic Receptor ◽  
Bioactive Molecules ◽  
Biological Behavior ◽  
Receptor Subtypes ◽  
Muscarinic Receptor Subtypes ◽  
Downstream Signaling ◽  
Colon Cancers ◽  
Research Findings ◽  
Cellular Machinery ◽  
Receptor Biology

Cancers arising from gastrointestinal epithelial cells are common, aggressive, and difficult to treat. Progress in this area resulted from recognizing that the biological behavior of these cancers is highly dependent on bioactive molecules released by neurocrine, paracrine, and autocrine mechanisms within the tumor microenvironment. For many decades after its discovery as a neurotransmitter, acetylcholine was thought to be synthesized and released uniquely from neurons and considered the sole physiological ligand for muscarinic receptor subtypes, which were believed to have similar or redundant actions. In the intervening years, we learned this former dogma is not tenable. (1) Acetylcholine is not produced and released only by neurons. The cellular machinery required to synthesize and release acetylcholine is present in immune, cancer, and other cells, as well as in lower organisms (e.g., bacteria) that inhabit the gut. (2) Acetylcholine is not the sole physiological activator of muscarinic receptors. For example, selected bile acids can modulate muscarinic receptor function. (3) Muscarinic receptor subtypes anticipated to have overlapping functions based on similar G protein coupling and downstream signaling may have unexpectedly diverse actions. Here, we review the relevant research findings supporting these conclusions and discuss how the complexity of muscarinic receptor biology impacts health and disease, focusing on their role in the initiation and progression of gastric, pancreatic, and colon cancers.

In Vivo Characterization of Muscarinic Receptor Subtypes That Mediate Vasodilatation in Patients With Essential Hypertension

Hypertension ◽  
1995 ◽  
Vol 26 (1) ◽  
pp. 70-77 ◽  
Author(s):  
Tobias A. Bruning ◽  
Peter C. Chang ◽  
Maarten G.C. Hendriks ◽  
Pieter Vermeij ◽  
Martin Pfaffendorf ◽  
...  
Keyword(s):  
Essential Hypertension ◽  
Muscarinic Receptor ◽  
Receptor Subtypes ◽  
Muscarinic Receptor Subtypes ◽  
In Vivo Characterization

Differential regulation of PI hydrolysis and adenylyl cyclase by muscarinic receptor subtypes

Nature ◽  
1988 ◽  
Vol 334 (6181) ◽  
pp. 434-437 ◽  
Author(s):  
Ernest G. Peralta ◽  
Avi Ashkenazi ◽  
John W. Winslow ◽  
J. Ramachandran ◽  
Daniel J. Capon
Keyword(s):  
Adenylyl Cyclase ◽  
Muscarinic Receptor ◽  
Differential Regulation ◽  
Receptor Subtypes ◽  
Muscarinic Receptor Subtypes ◽  
Pi Hydrolysis

Pre- and postjunctional muscarinic receptor subtypes in the vas deferens of rat

1994 ◽  
Vol 25 (8) ◽  
pp. 1643-1647 ◽  
Author(s):  
H.F. Miranda ◽  
E. Duran ◽  
D. Bustamante ◽  
C. Paeile ◽  
G. Pinardi
Keyword(s):  
Muscarinic Receptor ◽  
Vas Deferens ◽  
Receptor Subtypes ◽  
Muscarinic Receptor Subtypes

Location and quantification of muscarinic receptor subtypes in rat pons: implications for REM sleep generation

1997 ◽  
Vol 273 (3) ◽  
pp. R896-R904 ◽  
Author(s):  
H. A. Baghdoyan
Keyword(s):  
Muscarinic Receptor ◽  
Reticular Formation ◽  
Muscarinic Receptors ◽  
Rem Sleep ◽  
Binding Sites ◽  
Reticular Nucleus ◽  
Homogeneous Distribution ◽  
Receptor Subtypes ◽  
Pontine Reticular Formation ◽  
Muscarinic Receptor Subtypes

Microinjecting cholinomimetics into the pontine reticular formation produces a state that resembles natural rapid eye movement (REM) sleep. Evocation of this REM sleeplike states is anatomically site dependent within the pons and is mediated by muscarinic receptors. The cellular and molecular mechanisms underlying cholinergic REM sleep generation and muscarinic receptor subtype involvement remain to be specified. This study tested the hypothesis that muscarinic receptor subtypes are differentially distributed within the oral and caudal divisions of rat pontine reticular nucleus. In vitro receptor autoradiography was used to localize and quantify M1, M2, and M3 binding sites in the pontine reticular formation and in pontine brain stem regions known to regulate REM sleep. M1-M3 binding sites were present in some REM sleep-related nuclei, such as dorsal raphe and locus ceruleus. The pontine reticular formation was found to have a homogeneous distribution of M2 binding sites across its rostral to caudal extent, indicating that anatomic specificity of cholinergic REM sleep induction cannot be accounted for by a differential density of muscarinic receptors.

M2-Receptor Subtype Does Not Mediate Muscarine-Induced Increases in [Ca2+]i in Nociceptive Neurons of Rat Dorsal Root Ganglia

2000 ◽  
Vol 84 (4) ◽  
pp. 1934-1941 ◽  
Author(s):  
Rainer Haberberger ◽  
Reas Scholz ◽  
Wolfgang Kummer ◽  
Michaela Kress
Keyword(s):  
Receptor Antagonist ◽  
Muscarinic Receptor ◽  
Sensory Neurons ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Muscarinic Receptor Subtypes ◽  
Rt Pcr ◽  
Nociceptive Neurons

Multiple muscarinic receptor subtypes are present on sensory neurons that may be involved in the modulation of nociception. In this study we focused on the presence of the muscarinic receptor subtypes, M2 and M3 (M2R, M3R), in adult rat lumbar dorsal root ganglia (DRG) at the functional ([Ca2+]i measurement), transcriptional (RT-PCR), and translational level (immunohistochemistry). After 1 day in culture exposure of dissociated medium-sized neurons (20–35 μm diam) to muscarine was followed by rises in [Ca2+]i in 76% of the neurons. The [Ca2+]i increase was absent after removal of extracellular calcium and did not desensitize after repetitive application of the agonist. This rise in [Ca2+]i may be explained by the expression of M3R, which can induce release of calcium from internal stores via inositoltrisphospate. Indeed the effect was antagonized by the muscarinic receptor antagonist atropine as well as by the M3R antagonist, 4-diphenylacetoxy-N-(2 chloroethyl)-piperidine hydrochloride (4-DAMP). The pharmacological identification of M3R was corroborated by RT-PCR of total RNA and single-cell RT-PCR, which revealed the presence of mRNA for M3R in lumbar DRG and in single sensory neurons. In addition, RT-PCR also revealed the expression of M2R, which did not seem to contribute to the calcium changes since it was not prevented by the M2 receptor antagonist, gallamine. Immunohistochemistry demonstrated the presence of M2R and M3R in medium-sized lumbar DRG neurons that also coexpressed binding sites for the lectin I-B4, a marker for mainly cutaneous nociceptors. The occurrence of muscarinic receptors in putative nociceptive I-B4-positive neurons suggests the involvement of these acetylcholine receptors in the modulation of processing of nociceptive stimuli.

Muscarinic receptor subtypes in feline tracheal submucosal gland secretion

1992 ◽  
Vol 262 (2) ◽  
pp. L223-L228 ◽  
Author(s):  
H. Ishihara ◽  
S. Shimura ◽  
M. Satoh ◽  
T. Masuda ◽  
H. Nonaka ◽  
...  
Keyword(s):  
Muscarinic Receptor ◽  
Gland Secretion ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Submucosal Gland ◽  
Muscarinic Receptor Subtypes ◽  
Binding Assays ◽  
Submucosal Glands ◽  
Electrolyte Secretion ◽  
Quinuclidinyl Benzilate

To determine what muscarinic receptor subtype regulates [Ca2+]i mediating airway submucosal gland secretion, we examined the effects of atropine (Atr), pirenzepine (PZ), 11([2-(diethylamino)methyl-1-piperidinyl] acetyl)-5,11-dihydro-6H-pyrido (2,3-b)(1,4)-benzo-diazepin-6-one (AF-DX116) and 4-diphenylacetoxy-N-methyl-piperidine methiodide (4-DAMP) on methacholine (MCh)-evoked [Ca2+]i rise in acinar cells, and compared this with mucus glycoprotein (MGP) and electrolyte secretion evoked by MCh from submucosal glands isolated from feline trachea. [Ca2+]i was measured with the Ca(2+)-sensitive fluorescent dye, fura 2. We determined MGP secretion by measuring TCA-precipitable 3H-labeled glycoconjugates and electrolyte secretion by the change in the rate constant of 22Na-efflux from isolated glands. Half-maximal inhibitory concentrations (IC50) of PZ, AF-DX116, 4-DAMP, and Atr against MCh-evoked [Ca2+]i rise were 10(-7) M, 6 x 10(-6) M, 8 x 10(-9) M, and 6 x 10(-9) M, respectively. IC50 of PZ, AF-DX116, 4-DAMP, and Atr against MCh-evoked MGP secretion were 10(-6) M, 2 x 10(-5) M, 8 x 10(-9) M, and 6 x 10(-9) M, respectively. MCh (10(-5) M)-evoked 22Na efflux was significantly inhibited by 10(-7) M 4-DAMP and 10(-7) M Atr (P less than 0.01, each) but not by 10(-7) M PZ. Receptor binding assays with [3H]quinuclidinyl benzilate showed that the Ki values for PZ, AF-D x 116, 4-DAMP and Atr were 2.2 x 10(-8) M, 6.6 x 10(-7) M, 6.2 x 10(-10) M, and 2.9 x 10(-10) M, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Sign in / Sign up

Export Citation Format

Share Document