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Direct-Acting Cholinergic Agonists: Pharmacokinetics

Direct-Acting Cholinergic Agonists: Pharmacokinetics

Direct-acting cholinergic agonists, such as synthetic choline esters and naturally occurring alkaloids, exert their effects by enhancing the actions of acetylcholine and stimulating the parasympathetic nervous system. Synthetic choline esters share structural similarities with acetylcholine. For example, they have a positively charged quaternary ammonium or onium group, contributing to their hydrophilic characteristics. As a result, they are poorly absorbed in the body through oral...

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Indirect-acting cholinergic agonists, also known as anticholinesterases, exert their pharmacological effects by enhancing cholinergic transmission in various body parts, including the neuromuscular junction, autonomic cholinergic synapses, and the brain.
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Cholinergic agonists or cholinomimetics mimic the action of acetylcholine to stimulate the parasympathetic nervous system. They are categorized into direct-acting and indirect-acting agents. The direct-acting cholinergic drugs induce the parasympathetic response by directly binding to the muscarinic or nicotine receptors. In comparison, the indirect-acting cholinergic drugs prevent acetylcholine hydrolysis, indirectly contributing to the extended parasympathetic response.
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Direct-acting cholinergic agonists exert their pharmacological actions by mimicking the effects of acetylcholine on postsynaptic muscarinic receptors to generate parasympathetic responses. These agents elicit a range of physiological responses, including cardiovascular effects. For example, activation of muscarinic receptors induces bradycardia, decreased cardiac output, reduced peripheral resistance, and consequent hypotension. In the eye, stimulation of M3 receptors leads to smooth muscle...

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Direct-acting cholinergic agonists have many therapeutic uses in various medical fields. Choline esters, including acetylcholine, have limited clinical utility due to their non-selectivity and short duration of action. Still, acetylcholine and carbachol are applied topically during ophthalmologic surgery to induce miosis. Pilocarpine, a muscarinic and ganglionic stimulator, effectively treats open-angle glaucoma and alleviates xerostomia and dry mouth caused by radiotherapy or Sjögren syndrome.

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RETRACTED: Mancinelli et al. The Effects of Taurocholic Acid on Biliary Damage and Liver Fibrosis Are Mediated by Calcitonin-Gene-Related Peptide Signaling. <i>Cells</i> 2022, <i>11</i>, 1591.

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Updated: Jul 12, 2026

Partial Bile Duct Ligation in the Mouse: A Controlled Model of Localized Obstructive Cholestasis

Partial Bile Duct Ligation in the Mouse: A Controlled Model of Localized Obstructive Cholestasis

Published on: March 28, 2018

Biogenic amine actions on cholangiocyte function.

Sharon Demorrow¹, Heather Francis, Gianfranco Alpini

¹The Division of Research and Education, Medical Research Building, Scott and White Hospital, 702 S.W. H.K. Dodgen Loop, Temple, TX 76504,USA. demorrow@medicine.tamhsc.edu

Experimental Biology and Medicine (Maywood, N.J.)

|August 28, 2007

Summary

Biogenic amines regulate cellular functions. This review details their crucial roles in cholangiocyte secretion, apoptosis, and growth, impacting liver physiology and disease.

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Generation and Quantitative Characterization of Functional and Polarized Biliary Epithelial Cysts

Generation and Quantitative Characterization of Functional and Polarized Biliary Epithelial Cysts

Published on: May 16, 2020

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Partial Bile Duct Ligation in the Mouse: A Controlled Model of Localized Obstructive Cholestasis

Partial Bile Duct Ligation in the Mouse: A Controlled Model of Localized Obstructive Cholestasis

Published on: March 28, 2018

Generation and Quantitative Characterization of Functional and Polarized Biliary Epithelial Cysts

Generation and Quantitative Characterization of Functional and Polarized Biliary Epithelial Cysts

Published on: May 16, 2020

Area of Science:

Cellular biology
Neuroendocrinology
Gastroenterology

Background:

Biogenic amines, including serotonin, histamine, and dopamine, are key signaling molecules.
Cholangiocytes, the epithelial cells of the bile ducts, play vital roles in bile secretion and modification.
Dysregulation of cellular processes in cholangiocytes is implicated in various liver diseases.

Purpose of the Study:

To review the current understanding of biogenic amine signaling in cholangiocytes.
To elucidate the impact of these amines on cholangiocyte secretion, apoptosis, and growth.
To highlight the significance of biogenic amines in cholangiocyte physiology and pathophysiology.

Main Methods:

Literature review of studies investigating biogenic amines and cholangiocytes.
Analysis of research on biogenic amine receptors and their signaling pathways.
Synthesis of findings on the functional consequences for cholangiocytes.

Main Results:

Biogenic amines significantly influence cholangiocyte secretion.
These amines modulate apoptosis pathways in cholangiocytes.
Biogenic amines are critical regulators of cholangiocyte proliferation and growth.

Conclusions:

Biogenic amines are essential regulators of cholangiocyte function.
Understanding these pathways is crucial for addressing cholangiopathies.
Targeting biogenic amine signaling may offer therapeutic strategies for liver diseases.