Combined Inhibition of Histamine H1 Receptors and Leukotrienes Reduces Compound 48/80-Induced Contraction of the Human Bronchus in vitro.

Background/aims: Bronchial asthma continues to be a big challenge to therapy. Mast cells play an important role in allergic asthma. Histamine and leukotrienes are established mast cell mediators, but antihistamines currently play no role in asthma therapy.

Evidence that adrenergic and cholinergic but not capsaicin-sensitive nerves are involved in the nerve-mediated contraction of the guinea pig seminal vesicle.

Background/aims: The neurotransmitters participating in the nerve-mediated contraction of the guinea pig seminal vesicle (GPSV) have not been firmly established. There is debate as to the mediating role of norepinephrine and acetylcholine.

Methods: We have used longitudinally and circularly oriented strips of GPSV and activated their intramural nerves by electrical field stimulation (5 and 10 Hz for 30 s).

Purinoceptor-mediated, capsaicin-resistant excitatory effect of allyl isothiocyanate on neurons of the guinea-pig small intestine.

Allyl isothiocyanate (AITC; 200 μM) caused atropine- and tetrodotoxin-sensitive longitudinal muscle contraction on the guinea-pig small intestine. The response was not influenced by hexamethonium, a functional blockade of capsaicin-sensitive neurons or by antagonists acting at TRPV1 or TRPA1, but was abolished by the P2 purinoceptor antagonist PPADS (50 μM). It is concluded that cholinergic motoneurons are activated by a purinergic mechanism in the course of the AITC response, independently of capsaicin-sensitive processes or even TRPA1.

The contractile effect of anandamide in the guinea-pig small intestine is mediated by prostanoids but not TRPV1 receptors or capsaicin-sensitive nerves.

Although exogenous and endogenous cannabinoid receptor agonists have well-documented inhibitory effects on gastrointestinal motility, a TRPV1 receptor-mediated excitatory action of anandamide (arachidonoyl ethanolamide, AEA) in the guinea-pig ileum strip has also been described. We used in vitro capsaicin desensitization for assessing the possible participation of sensory neurons in the contractile effect of anandamide on the guinea-pig whole ileum, as well as autonomic drugs and a cyclooxygenase inhibitor for characterizing this response. Isolated organ experiments were used with isotonic recording.