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Serotonin‐induced increase in cAMP in ganglia isolated from the myenteric plexus of the guinea pig small intestine: Mediation by a novel 5‐HT receptor
Author(s) -
FioricaHowells Elena,
Wade Paul R.,
Gershon Michael D.
Publication year - 1993
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.890130406
Subject(s) - myenteric plexus , serotonin , guinea pig , 5 ht receptor , mediation , biology , neuroscience , receptor , medicine , endocrinology , pharmacology , anatomy , immunohistochemistry , political science , law
Serotonin (5‐HT) is a mediator (through 5‐HT 1P receptors) of slow EPSPs in myenteric ganglia of the small intestine. The effect of 5‐HT can be mimicked by elevating cAMP; therefore, we tested the hypothesis that the slow EPSP‐like response to 5‐HT is cAMP‐mediated. Guinea pig gut was enzymatically dissociated; myenteric ganglia remained intact and were collected by filtration. Neurons in the isolated ganglia retained their ability to manifest the slow EPSP‐like response to 5‐HT. Exposure to 5‐HT raised the ganglionic level of cAMP (ED 50 0.3 μM). This effect was not antagonized by the 5‐HT 1P antagonist, N‐acetyl‐5‐hydroxytryptophyl‐5‐hydroxytryptophan amide (100.0 μM), or mimicked by the 5‐HT 1P agonist, 5‐hydroxyindalpine (10.0 μM). Increases in cAMP were also evoked by the 5‐HT 1 agonist, 5‐carboxyamidotryptamine (10.0 μM), the 5‐HT 2 agonist, (±)‐1‐(2,5‐dimethoxy‐4‐iodophenyl)‐2‐aminopropane (DOI; 1.0–10.0 μM), and by the 5‐HT 4 agonists, renzapride (1.0–10.0 μM) and 5‐methoxytryptamine (1.0–10.0 μM); however, neither the 5‐HT 1 /5‐HT 2 antagonists, spiperone, methysergide, and methiothepin, nor the 5‐HT 4 antagonist, tropisetron (ICS 205–930; 10.0 μM), were able to inhibit the rise in cAMP evoked by these compounds or by 5‐HT (0.1–10.0 μM). The 5‐HT‐evoked elevation of cAMP was antagonized by ketanserin (10.0 μM), which also blocked the effects of 5‐methoxytryptamine and DOI, but not those of renzapride. The effective concentration of DOI, however, was higher than that needed for activation of 5‐HT 2 receptors, and Northern analysis using a cDNA probe encoding the rat 5‐HT 2 receptor failed to reveal the presence of 5‐HT 2 mRNA in myenteric ganglia, although it hybridizes with mRNA of the right size in the guinea pig brain. Compounds that failed to change levels of cAMP or to antagonize the action of 5‐HT included 8‐hydroxy‐di‐ n ‐propylamino tetralin, R58639, R88226, and sumatriptan. It is concluded that the receptor responsible for the 5‐HT‐induced rise in cAMP in ganglia isolated from the guinea pig myenteric plexus is not a known subtype of 5‐HT receptor. Since the pharmacology of this novel receptor is different from that of the slow EPSP‐like response to 5‐HT, the receptor probably does not mediate the slow EPSP. © 1993 Wiley‐Liss, Inc.