PMID- 7515096
OWN - NLM
STAT- MEDLINE
DCOM- 19940624
LR  - 20190516
IS  - 0741-5400 (Print)
IS  - 0741-5400 (Linking)
VI  - 55
IP  - 6
DP  - 1994 Jun
TI  - Differential effects of cAMP-elevating drugs on stimulus-induced cytosolic 
      calcium changes in human basophils.
PG  - 798-804
AB  - Drugs that elevate cAMP levels in human basophils are known to inhibit 
      immunoglobulin E (IgE)-mediated histamine release. We have examined whether 
      cAMP-active agents inhibit the cytosolic Ca2+, [Ca2+]i, response that normally 
      accompanies activation of basophils. As previously described, this [Ca2+]i 
      response is biphasic, one phase dependent on internal sources of calcium and a 
      second later phase dependent on extracellular calcium, as observed in many cell 
      types. Forskolin and rolipram or their combination had no effect on the initial 
      elevation of cytosolic calcium that follows stimulation with anti-IgE antibody. 
      In contrast, the second phase of the IgE-mediated calcium response was inhibited 
      by these agents. For IgE-mediated responses, the relative efficacy of various 
      cAMP active agents (rolipram approximately forskolin < dibutyryl cAMP < forskolin 
      + rolipram) for the inhibition of histamine release and the second-phase calcium 
      response was similar and roughly paralleled the measured increase in basophil 
      cAMP. In contrast, neither the first nor the second phase of the f-Met-Leu-Phe 
      (fMLP)-induced calcium response was inhibited by any of the cAMP-active agents 
      tested. Indeed, at low concentrations of fMLP, a combination of forskolin and 
      rolipram caused slight enhancement of the calcium response. This result was 
      consistent with the observations that these agents had no effect or caused slight 
      enhancement of histamine or leukotriene released induced by fMLP. Similarly, 
      cAMP-active agents caused no inhibition of C5a or phorbol ester (phorbol 
      myristate acetate)-induced histamine release. These observations suggest that 
      inhibition of the phase of the calcium response that is dependent on 
      extracellular calcium could account for the inhibition of histamine release by 
      these agents. However, these studies also suggested that (1) this is effect is 
      not exerted at the level of the inositol trisphosphate (InsP3) receptor or InsP3 
      metabolism and (2) the mechanisms that maintain the second-phase calcium response 
      are possibly distinct for IgE- and fMLP-mediated reactions because cAMP-active 
      agents inhibited the second-phase response of only one stimulus.
FAU - Botana, L M
AU  - Botana LM
AD  - Johns Hopkins Asthma and Allergy Center, Baltimore, Maryland 21224.
FAU - MacGlashan, D W
AU  - MacGlashan DW
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - J Leukoc Biol
JT  - Journal of leukocyte biology
JID - 8405628
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Fluorescent Dyes)
RN  - 0 (Leukotrienes)
RN  - 0 (Pyrrolidinones)
RN  - 105344-37-4 (fura-2-am)
RN  - 1F7A44V6OU (Colforsin)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine)
RN  - E0399OZS9N (Cyclic AMP)
RN  - K676NL63N7 (Rolipram)
RN  - SY7Q814VUP (Calcium)
RN  - TBT296U68M (1-Methyl-3-isobutylxanthine)
RN  - TSN3DL106G (Fura-2)
SB  - IM
MH  - 1-Methyl-3-isobutylxanthine/*pharmacology
MH  - Anti-Inflammatory Agents, Non-Steroidal/pharmacology
MH  - Basophils/drug effects/metabolism/*physiology
MH  - Calcium/*blood
MH  - Colforsin/*pharmacology
MH  - Cyclic AMP/*blood
MH  - Cytosol/metabolism
MH  - Fluorescent Dyes
MH  - Fura-2/analogs & derivatives
MH  - Histamine Release/*drug effects
MH  - Humans
MH  - Immunoglobulin E/*pharmacology
MH  - In Vitro Techniques
MH  - Kinetics
MH  - Leukotrienes/blood
MH  - Microscopy, Fluorescence
MH  - N-Formylmethionine Leucyl-Phenylalanine/pharmacology
MH  - Pyrrolidinones/pharmacology
MH  - Rolipram
MH  - Time Factors
EDAT- 1994/06/01 00:00
MHDA- 1994/06/01 00:01
CRDT- 1994/06/01 00:00
PHST- 1994/06/01 00:00 [pubmed]
PHST- 1994/06/01 00:01 [medline]
PHST- 1994/06/01 00:00 [entrez]
AID - 10.1002/jlb.55.6.798 [doi]
PST - ppublish
SO  - J Leukoc Biol. 1994 Jun;55(6):798-804. doi: 10.1002/jlb.55.6.798.