PMID- 1599509
OWN - NLM
STAT- MEDLINE
DCOM- 19920708
LR  - 20231213
IS  - 0006-2952 (Print)
IS  - 0006-2952 (Linking)
VI  - 43
IP  - 10
DP  - 1992 May 28
TI  - Inhibition of mast cell secretion by oxidation products of natural polyamines.
PG  - 2237-45
AB  - Mast cells secrete many biologically active compounds upon stimulation by 
      immunoglobulin E (IgE) and specific antigen (Ag), anaphylatoxins, as well as a 
      number of cationic compounds which include drugs, kinins and neuropeptides. The 
      effects of the two naturally occurring polyamines, spermine (SP) and spermidine 
      (SPD), on mast cell secretion were studied because they have been implicated in 
      the modulation of cellular processes, possibly through their cationic charge or 
      the regulation of calcium ions. SP and SPD over the range of 10(-7) to 10(-4) M 
      inhibited the release of 5-hydroxytryptamine (5-HT, serotonin) triggered by 
      compound 48/80 (C48/80) in a time- and concentration-dependent manner, as long as 
      at least 2% calf serum (CS) was present. SP also inhibited secretion of both 
      histamine and serotonin stimulated immunologically by using IgE and anti-rat IgE. 
      This inhibition was not accompanied by cytotoxicity. The major available 
      polyamine metabolites tested, N1-acetyl spermine (N1-acSP) and N8-acetyl 
      spermidine (N8-acSPD), also showed inhibition in the presence of CS, whereas 
      putrescine, N8,N1-hexamethylene-bis-acetamide (HMBA) and benzylamine did not. 
      Fetal bovine serum (FBS), as well as human and rat serum, which do not contain 
      polyamine oxidase, did not result in any inhibition with the polyamines tested. 
      Inhibitors of the polyamine oxidase blocked the polyamine effect, indicating that 
      the inhibition of mast cell secretion must derive from aldehydes produced from 
      these polyamines. Addition of the aldehyde inhibitor phenylhydrazine (phi-HDZ), 
      simultaneously with, but not following the polyamines, blocked their inhibitory 
      effect, further strengthening the involvement of aldehydes. These results 
      indicate that naturally occurring polyamines may regulate mast cell secretion 
      through metabolic products of polyamine oxidase, a similar enzyme of which is 
      also present in human liver, placenta and pregnant serum.
FAU - Vliagoftis, H
AU  - Vliagoftis H
AD  - Department of Pharmacology and Experimental Therapeutics, Tufts University School 
      of Medicine, Boston, MA 02111.
FAU - Boucher, W S
AU  - Boucher WS
FAU - Mak, L L
AU  - Mak LL
FAU - Theoharides, T C
AU  - Theoharides TC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 2FZ7Y3VOQX (Spermine)
RN  - 333DO1RDJY (Serotonin)
RN  - 4091-50-3 (p-Methoxy-N-methylphenethylamine)
RN  - EC 1.5.- (Oxidoreductases Acting on CH-NH Group Donors)
RN  - U87FK77H25 (Spermidine)
SB  - IM
MH  - Animals
MH  - Cattle
MH  - Dose-Response Relationship, Drug
MH  - Humans
MH  - Male
MH  - Mast Cells/*drug effects/metabolism
MH  - Oxidation-Reduction
MH  - Oxidoreductases Acting on CH-NH Group Donors/metabolism
MH  - Rats
MH  - Rats, Inbred Strains
MH  - Serotonin/metabolism
MH  - Spermidine/metabolism/*pharmacology
MH  - Spermine/metabolism/*pharmacology
MH  - p-Methoxy-N-methylphenethylamine/*pharmacology
MH  - Polyamine Oxidase
EDAT- 1992/05/28 00:00
MHDA- 1992/05/28 00:01
CRDT- 1992/05/28 00:00
PHST- 1992/05/28 00:00 [pubmed]
PHST- 1992/05/28 00:01 [medline]
PHST- 1992/05/28 00:00 [entrez]
AID - 0006-2952(92)90183-J [pii]
AID - 10.1016/0006-2952(92)90183-j [doi]
PST - ppublish
SO  - Biochem Pharmacol. 1992 May 28;43(10):2237-45. doi: 10.1016/0006-2952(92)90183-j.