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Somatostatin inhibits cAMP-mediated cholinergic transmission in the myenteric plexus
1Department of Internal Medicine, University of Michigan Medical School, Ann Arbor 48109-0362.
Abstract:
The mechanism by which somatostatin acts to modulate cholinergic transmission is not clear. In this study we investigated the role of the adenosine 3',5'-cyclic monophosphate (cAMP) system in mediating cholinergic transmission in the guinea pig myenteric plexus and examined the ability of somatostatin to alter acetylcholine (ACh) release stimulated by various cAMP agonists. Forskolin, 8-bromo-cAMP, vasoactive intestinal peptide (VIP), and cholera toxin each stimulated the release of [3H]ACh in a dose-related manner. Addition of theophylline enhanced the release of [3H]ACh stimulated by these cAMP agonists. In contrast 2',5'-dideoxyadenosine, an inhibitor of adenylate cyclase, antagonized the action of forskolin, VIP, and cholera toxin but had no effect on that evoked by 8-bromo-cAMP. These observations suggest that cAMP may serve as a physiological mediator for ACh release from myenteric neurons. Somatostatin inhibited release of [3H]ACh evoked by various cAMP agonists in a dose-related manner. Maximal inhibition, observed in the presence of 10(-6) M somatostatin was 48 +/- 5, 47 +/- 9, and 43 +/- 12% of control for forskolin-, VIP-, and cholera toxin-evoked release of [3H]ACh. In contrast somatostatin at 10(-6) M inhibited only 20 +/- 5% of the release of [3H]ACh stimulated by 8-bromo-cAMP. Pretreatment with pertussis toxin antagonized the inhibitory effect of somatostatin on the release of [3H]ACh evoked by forskolin, VIP, or cholera toxin but had no effect on the inhibitory action of somatostatin on the release of [3H]ACh evoked by 8-bromo-cAMP.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
This study reveals that adenosine 3
Area of Science:
- Neuroscience
- Gastroenterology
Background:
- The precise mechanism of somatostatin's modulation of cholinergic transmission remains unclear.
- Cholinergic transmission in the myenteric plexus plays a crucial role in gastrointestinal function.
Purpose of the Study:
- To investigate the role of the adenosine 3',5'-cyclic monophosphate (cAMP) system in mediating cholinergic transmission.
- To examine how somatostatin affects acetylcholine (ACh) release stimulated by cAMP agonists.
Main Methods:
- Utilized guinea pig myenteric plexus preparations.
- Administered various cAMP agonists (forskolin, 8-bromo-cAMP, VIP, cholera toxin) and somatostatin.
- Assessed the release of [3H]acetylcholine ([3H]ACh).
- Employed pertussis toxin pretreatment to investigate signaling pathways.
Main Results:
- cAMP agonists (forskolin, 8-bromo-cAMP, VIP, cholera toxin) dose-dependently stimulated [3H]ACh release.
- Somatostatin inhibited [3H]ACh release evoked by cAMP agonists, with varying efficacy.
- Pertussis toxin pretreatment antagonized somatostatin's inhibition of forskolin-, VIP-, and cholera toxin-evoked release, but not 8-bromo-cAMP-evoked release.
Conclusions:
- cAMP likely acts as a physiological mediator for ACh release from myenteric neurons.
- Somatostatin's inhibitory effect on ACh release involves a pertussis toxin-sensitive pathway, suggesting G-protein involvement.
- The differential effects of somatostatin on cAMP-mediated ACh release highlight complex regulatory mechanisms.