The contractile response of the guinea pig vas deferens to motor nerve stimulation is biphasic. The first phase is antagonized by the specific adenosine triphosphate-receptor antagonist arylazido aminoproprionyl adenosine triphosphate (ANAPP3), and the second by the alpha-receptor antagonist prazosin. The underlying electrical event, the excitatory junction potential, is also blocked by ANAPP3, but not by prazosin.

Dey. Interleukin-1␤-induced airway hyperresponsiveness enhances substance P in intrinsic neurons of ferret airway. Am J Physiol Lung Cell Mol Physiol 283: L909-L917, 2002. First published April 12, 2002 10.1152/ajplung.00363.2001.-Interleukin (IL)-1␤ causes airway inflammation, enhances airway smooth muscle responsiveness, and alters neurotransmitter expression in sensory, sympathetic, and myenteric neurons. This study examines the role of intrinsic airway neurons in airway hyperresponsiveness (AHR) induced by IL-1␤. Ferrets were instilled intratracheally with IL-1␤ (0.3 g/0.3 ml) or saline (0.3 ml) once daily for 5 days. Tracheal smooth muscle contractility in vitro and substance P (SP) expression in tracheal neurons were assessed. Tracheal smooth muscle reactivity to acetylcholine (ACh) and methacholine (MCh) and smooth muscle contractions to electric field stimulation (EFS) both increased after IL-1␤. The IL-1␤-induced AHR was maintained in tracheal segments cultured for 24 h, a procedure that depletes SP from sensory nerves while maintaining viability of intrinsic airway neurons. Pretreatment with CP-99994, an antagonist of neurokinin 1 receptor, attenuated the IL-1␤-induced hyperreactivity to ACh and MCh and to EFS in cultured tracheal segments. SP-containing neurons in longitudinal trunk, SP innervation of superficial muscular plexus neurons, and SP nerve fiber density in tracheal smooth muscle all increased after treatment with IL-1␤. These results show that IL-1␤-enhanced cholinergic airway smooth muscle contractile responses are mediated by the actions of SP released from intrinsic airway neurons. airway inflammation; airway smooth muscle contraction; muscarinic agonists; neurokinin receptor; airway innervation

Arylazido aminopropionyl adenosine triphosphate (ANAPP3), a photoaffinity label, antagonized specifically adenine nucleotide-induced contractions of the guinea pig vas deferens. Irradiation of tissues with visible light in the presence of ANAPP3 resulted in an irreversible antagonism, which was prevented when adenosine triphosphate was present. In the absence of light, the antagonism was reversible and may have resulted from an autoinhibition phenomenon. Responses to acetylcholine, histamine, norepinephrine, and potassium chloride were not affected by ANAPP3.