Desensitization of muscarinic receptor-coupled phosphoinositide hydrolysis in rat hippocampus: comparisons with the alpha 1-adrenergic response.

Abstract:

:In the presence of lithium, carbamylcholine chloride (carbachol) and epinephrine increase the accumulation of inositol monophosphate severalfold in hippocampal slices from the rat. The stimulation by carbachol (EC50, 31 microM) is mediated by muscarinic receptors, whereas the effects of epinephrine (EC50, 2 microM) are due to activation of alpha 1-adrenergic receptors. The responses of epinephrine and carbachol are additive, even under conditions that significantly reduce the levels of phosphoinositides and free inositol, suggesting that the muscarinic and adrenergic receptors may be located on separate cells. At concentrations that saturate their respective receptors, epinephrine induces an increase in inositol monophosphate that is linear with time to at least 60 min, whereas the response to carbachol begins to reach a plateau by 20-40 min. When hippocampal slices are preincubated with saturating concentrations of carbachol, the subsequent response to carbachol is reduced by 42%. However, preincubation with carbachol or epinephrine has no effect on the subsequent response to epinephrine. Despite the lack of adrenergic desensitization by this paradigm, preexposure of hippocampal slices to the tumor-promoting phorbol ester, phorbol 12,13-dibutyrate, reduces the response to epinephrine to a significantly greater degree (57%) than it reduces the muscarinic response (25%). These studies indicate that, although they utilize the same second messenger, the muscarinic and alpha 1-adrenergic receptors of hippocampal slices have different characteristics and regulatory mechanisms.

journal_name

J Neurochem

authors

Lenox RH,Hendley D,Ellis J

doi

10.1111/j.1471-4159.1988.tb02947.x

subject

Has Abstract

pub_date

1988-02-01 00:00:00

pages

558-64

issue

2

eissn

0022-3042

issn

1471-4159

journal_volume

50

pub_type

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