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PMID: 2547479 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Inhibition of histamine-stimulated inositol phospholipid hydrolysis by agents which increase cyclic AMP levels in bovine tracheal smooth muscle.

British journal of pharmacology ·Vol. 97 ·No. 2 ·1989-06-00 ·Pages 603-13

Hall IP, Donaldson J, Hill SJ

Abstract

1. The effect on histamine-stimulated [3H]-inositol phosphate accumulation of a range of agents which increase the accumulation, or mimic the actions, of cyclic AMP has been investigated in bovine tracheal smooth muscle. 2. Salbutamol (1 microM), forskolin (1 microM) and vasoactive intestinal peptide (VIP, 1 microM) inhibited the inositol phosphate response to 0.1 mM histamine and increased the accumulation of [3H]-cyclic AMP in [3H]-adenine-labelled slices of bovine tracheal smooth muscle. The effect on inositol phospholipid hydrolysis was mimicked by the membrane permeant analogues of cyclic AMP, dibutrylcyclic AMP (1 mM) and 8-bromo-cyclic AMP (1 mM). 3. In contrast to salbutamol, which was equally effective at producing the two effects, forskolin produced large increases in [3H]-cyclic AMP accumulation (EC50 = 1.2 microM) at much higher concentrations than those required for inhibition of histamine-stimulated [3H]-inositol phosphate accumulation (EC50 = 0.09 microM). However, significant increases in [3H]-cyclic AMP accumulation, of similar magnitude to those obtained with salbutamol and VIP, were observed over the concentration range appropriate for inhibition of the inositol phosphate response to histamine. 4. In the presence of histamine (0.1 mM), isobutylmethylxanthine (IBMX, 1 mM) and rolipram (0.1 mM) both significantly (P less than 0.05) elevated tissue [3H]-cyclic AMP levels. IBMX, rolipram and (to a lesser extent) SKF 94120 significantly (P less than 0.05) reduced histamine-stimulated [3H]-inositol phosphate accumulation by 81%, 68% and 20%, respectively. M&B 22948 was without a significant effect on either [3H]-cyclic AMP or histamine-induced [3H]-inositol phosphate accumulation. 5. Both rolipram and forskolin reduced the increase in incorporation of [3H]-inositol into membrane phospholipids which followed stimulation with histamine. However, a significant inhibition of [3H]-inositol phosphate accumulation could be demonstrated under conditions in which there was no change in the level of [3H]-inositol incorporation.

MeSH Terms
8-Bromo Cyclic Adenosine Monophosphate/pharmacology Adenine/metabolism Albuterol/pharmacology Animals Bucladesine/pharmacology Cattle Colforsin/pharmacology Cyclic AMP/analogs & derivatives,metabolism Histamine/pharmacology Histamine Antagonists Hydrolysis In Vitro Techniques Inositol Phosphates/metabolism Muscle, Smooth/drug effects,metabolism Phosphodiesterase Inhibitors/pharmacology Pyrrolidinones/pharmacology Rolipram Sugar Phosphates/metabolism Trachea/drug effects,metabolism Vasoactive Intestinal Peptide/pharmacology
Chemicals
Histamine Antagonists Inositol Phosphates Phosphodiesterase Inhibitors Pyrrolidinones Sugar Phosphates Colforsin 8-Bromo Cyclic Adenosine Monophosphate Vasoactive Intestinal Peptide Bucladesine Histamine Cyclic AMP Adenine Rolipram Albuterol
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Hall I P
Department of Physiology and Pharmacology, Medical School, Queen's Medical Centre, Nottingham.
Donaldson J
Hill S J
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Article Info
Journal
British journal of pharmacology
Abbr.
Br J Pharmacol
ISSN
0007-1188
DOI
10.1111/j.1476-5381.1989.tb11992.x
Published
1989-06-00
Pages
603-13
Language
English
Region
England
NLM ID
7502536
PMCID
PMC1854535
Subset
IM
Grants
Wellcome Trust · United Kingdom
External Links
PubMed source DOI: 10.1111/j.1476-5381.1989.tb11992.x PMC Full Text View journal details
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