Effects of Some Purine Derivatives on the Guinea‐pig Trachea and Their Interaction With Drugs That Block Adenosine Uptake

Abstract

I Adenosine, adenosine 5'-triphosphate (ATP), adenine, inosine and guanosine all caused concentration-dependent relaxations of guinea-pig tracheal smooth muscle in vitro. The relative potencies in descending order were: adenine > guanosine > inosine > adenosine > ATP 2 Responses to the purine compounds were unaffected by propranolol (1 jg/ml). 3 The spasmolytic potencies of adenosine and ATP were greatly enhanced in the presence of the adenosine uptake blocking drugs dipyridamole, hexobendine or Dilazep, whereas responses to adenine were unaffected and those to inosine and guanosine were reduced. 4 The spasmolytic potencies of noradrenaline, aminophylline, prostaglandin E2 and glyceryl trinitrate were unaffected by dipyridamole, hexobendine and Dilazep. 5 It is suggested that an adenosine uptake process may exist in the trachea of the guinea-pig and that this process is inhibited by dipyridamole, hexobendine and Dilazep.

The Development of Tachyphylaxis to Electrical Stimulation in Guinea‐pig Ileal Longitudinal Muscles and the Possible Participation of Adenosine and Adenine Nucleotides

“…In contrast, dipyridamole and hexobendine have been shown to potentiate the inhibitory effect of adenosine and adenine nucleotide in the heart, intestine and trachea (Stafford, 1966;Kolassa, Pfleger & Rummel, 1970; At arrow, theophylline 30 gM was added to the superfusion solution. Satchell et al, 1972;Coleman, 1976). Our previous experiments with guinea-pig ileum demonstrated that the inhibitory effect of adenosine on cholinergic nerves was specifically antagonized by theophylline and potentiated by dipyridamole and hexobendine.…”

Inhaled adenosine and guanosine on airway resistance in normal and asthmatic subjects.

“…This is the first study to define the pharmacological activity of adenosine on human airways. There have been many in vitro studies to show that adenosine and its modified purine analogues are capable of relaxing gastrointestinal (Ally & Nakatsu, 1976), vascular (Herlihy et al, 1976) and tracheal (Coleman, 1976) smooth muscle preparations. However, in asthma, rather than showing a relaxant response adenosine is a powerful bronchoconstrictor.…”

“…If adenosine antagonism is relevant to theophylline's effect on the airways in asthma, then adenosine should be a bronchoconstrictor (Fredholm, 1980a). In animal isolated tracheal and bronchial airway preparations whose tone has been artificially increased, adenosine causes relaxa-0306-5251/83/0200-1610 $02.00 tion (Fredholm et al, 1979;Coleman, 1976;Farmer & Farrar, 1976) whereas, in preparations of guineapig trachea with normal intrinsic tone, adenosine causes a weak but consistent contraction (Fredholm et al, 1979;Advenier et al, 1982). To extend the observations to man, we have investigated the effect of adenosine and the related nucleoside, guanosine, on the airways of normal and asthmatic subjects in vivo.…”

The epithelium and the pharmacology of guinea‐pig tracheal tone in vitro

“…Adenosine may produce both a slight contraction (at low concentrations) and a relaxation of guinea-pig tracheae in vitro (Coleman, 1976). Holroyde (1986) reported contractions to adenosine only in epithelium-denuded tracheal preparations.…”