Immunological Release of Histamine and Slow Reacting Substance of Anaphylaxis From Human Lung

Abstract

The immunologic release of histamine and slow reacting substance of anaphylaxis (SRS-A) from human lung tissue can be enhanced by stimulation with either alpha adrenergic agents (phenylephrine or norepinephrine in the presence of propranolol) or cholinergic agents (acetylcholine or Carbachol). The finding that atropine prevents cholinergic but not comparable alpha adrenergic enhancement is consistent with the view that cholinergic and alpha adrenergic agonists interact with separate receptor sites on the target cells involved in the immunologic release of chemical mediators. The consistent qualitative relationship between the antigen-induced release of mediators and the level of cyclic adenosine monophosphate (cyclic AMP) as measured by the isolation of 14C-labeled cyclic AMP after incorporation of adenine-14C into the tissues or by the cyclic AMP binding protein assay suggests that changes in the level of this cyclic nucleotide mediate adrenergic modulation of the release of histamine and SRS-A. The addition of 8-bromo-cyclic guanosine monophosphate (cyclic GMP) produces an enhancement of the immunologic release of mediators while dibutyryl cyclic AMP is inhibitory. As cholinergic-induced enhancement was not associated with a measurable change in the levels of cyclic AMP, the possibility is suggested that cyclic GMP may be the intracellular mediator of cholinergic-induced enhancement of the immunologic release of histamine and SRS-A.

Anti-anaphylactic activities of a new benzopyranopyridine derivative Y-12,141 in rats and guinea pigs.

“…An N-isopropyl acid ester of atropine (Sch 1000) causes a significant bronchodilation in asthmatic subjects (17). Immunologic release of histamine and SRS-A from human lung tissue can be enhanced by stimulation with cholinergic agents (acetyl choline or carbachol) in vitro, and this release is inhibited by atropine (18). Acethylcholine causes a release of histamine from rat mast cells (19).…”

Human Lung Tissue and Anaphylaxis

“…Increased levels of cyclic GMP which have been observed in human lung tissue after cholinergic stimulation and PGF2 incubation (16,17) were found to prevent cold-induced microtubular disassembly. By inference, increased levels of cyclic GMP favor the polymerized state of microtubular assembly and thereby may facilitate the immunologically induced movement of secretory granules along an increased microtubular framework.…”

“…Increased intracellular cyclic GMP in human lung tissue which occurs after adding exogenous cyclic GMP (16) and after addition of cholinergic agonists or prostaglandin F, (16,17) is associated with marked augmentation of the antigen-induced secretory reaction. The possibility that the effect of increased levels of cyclic GMP might be generated by an interaction with microtubules was explored.…”

“…Indeed, cyclic AMP exerts a general inhibitory influence upon diverse immuno-logic effector systems (14,15). Increases in cyclic guanosine 3',5'-monophosphate (cyclic GMP) enhance the antigen-initiated secretion of mediators from lung tissue (16,17) and nasal mucosa (12), and may partially prevent the inhibitory effects of cyclic AMP (18). The site of action of these cyclic nucleotides in modulating the secretion ofmediators remains unclear although in other systems there are well-described morphologic (19)(20)(21)(22) and biochemical (23)(24)(25)(26) interactions between cyclic AMP and microtubules.…”

“…J.). The dried eluates were resuspended in 1.0 ml sodium acetate buffer (50 mM, pH 4.0) and the cyclic AMP content determined by the protein binding assay (30) as described (16). Recovery of cyclic AMP was monitored by cyclic [14C]AMP added to the perchloric acid and was 75-90%.…”