The mechanism of action of soluble lymphocyte mediators. V. Mechanism of refractoriness to adenylate cyclase stimulators induced by migration inhibitory factor (MIF)

Edgar Pick*, Anna Grunspan-Swirsky

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Exposure of purified guinea pig macrophages to lymphocyte culture supernatants, containing migration inhibitory factor (MIF), for a minimum of 1 hr results in reduced cyclic 3′,5′-adenosine monophosphate (cAMP) accumulation in response to adenylate cyclase stimulators, which persists for at least 6 hr. MIF-induced refractoriness is not due to: inactivation of the stimulating agents, destruction of membrane receptors, excessive leakage of cAMP from the cells, or activation of cAMP phosphodiesterase. Refractoriness develops normally in the absence of protein synthesis. It is concluded that MIF-induced refractoriness is an expression of diminished cAMP synthesis. However, MIF does not directly inhibit basal or stimulated adenylate cyclase, nor are prostaglandin synthesis intermediates responsible for the reduced cAMP production. Evidence is presented in support of the proposal that MIF interferes with the signal transfer from membrane receptors to the enzyme by an effect on cytoplasmic microtubules.

Original languageEnglish
Pages (from-to)340-349
Number of pages10
JournalCellular Immunology
Volume32
Issue number2
DOIs
StatePublished - Aug 1977

Funding

FundersFunder number
F. Hoffmann-LaRoche & Co. Ltd.
U.S.-Israel Binational Science Foundation
National Institutes of Health

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