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

Abstract

Electrically (30 Hz) induced contractions of guinea‐pig isolated ileal longitudinal muscles were reduced by tetrodotoxin (1 μm), atropine (1 μm), adenosine (30 μm) and morphine (10 μm). When stimulated with 10 or 30 Hz for 10 s at 1 min intervals, a progressive decline of amplitude of the contraction was seen (development of tachyphylaxis). At this time, the contractile response to 1,1‐dimethyl‐4‐phenylpiperazinium iodide (DMPP) (10 μm) was also greatly reduced. The smaller responses to electrical stimulation and DMPP during tachyphylaxis were restored to their initial amplitude by the addition of theophylline (10 μm). The appearance of tachyphylaxis was prevented by pretreatment with theophylline (1 to 10 μm) and was greatly accelerated by pretreat‐ment with dipyridamole (0.1, 1 μm). In [14C]‐choline or [3H]‐adenosine preloaded muscle strips, electrical stimulation (30 Hz) increased the 14C‐ or 3H‐output, the effect being sensitive to tetrodotoxin blockade. The tachyphylaxis to electrical stimulation was accompanied by a considerable and sustained increase in 3H‐output, an effect that was accelerated by dipyridamole (1 μm). The 14C‐output initially increased but fell off gradually with the development of tachyphylaxis at which time theophylline (30 1) reversed the fall. There was a marked increase in the proportion of released [3H]‐adenosine to its derivatives during the development of tachyphylaxis. Approximately 60% of the released total radioactivity after tachyphylaxis was found to be [3H]‐adenosine. These results suggest that the development of tachyphylaxis may be closely associated with the release of endogenous adenosine derivatives (mostly adenosine) which have presynaptic inhibitory actions on the cholinergic elements in guinea‐pig ileum.

Effects of Adenosine on Contractile Response of Circular Muscle in Electrically Stimulated Guinea-Pig Ileum

“…It is proposed that endogenous adenosine-related compounds may have physiological roles as modulators which control acetylcholine release in the circular muscle of guinea-pig ileum, in agreement with our suggestions (16,17) and the other reports (4,18).…”

Contribution of Prostaglandins to the Adenosine Triphosphate‐induced Contraction of Rabbit Urinary Bladder

“…It thus seems plausible that the presence (release) of prostaglandins plays a role in the size of the electrically induced contractions (Burnstock et al, 1978a), while tachyphylaxis to exogenous ATP is still present. This may be caused by adenosine accumulation (Hayashi, Kunimoto, Mori, Shinozuka & Yamada 1978), which might decrease the contractile response to exogenous ATP (Sjogren & Andersson 1979).…”

Blockade of Striatal Neurone Responses to Morphine by Aminophylline: Evidence for Adenosine Mediation of Opiate Action

“…There is evidence that adenosine may be involved in the responses to morphine. Both morphine and adenosine inhibit transmitter release (Ginsborg & Hirst, 1972;Hedqvist & Fredholm, 1976;Hayashi, Kunitoko, Mori, Shinozuka & Yamada, 1978) and both drug actions can be blocked by theophylline (Sawynok & Jhamandas, 1976). Conversely, dipyridamole, an inhibitor of the adenosine uptake (Huang & Daly, 1974) potentiates the inhibition of transmitter release by both adenosine and morphine (Gintzler & Musacchio 1975;Hayashi et al, 1978).…”

“…Both morphine and adenosine inhibit transmitter release (Ginsborg & Hirst, 1972;Hedqvist & Fredholm, 1976;Hayashi, Kunitoko, Mori, Shinozuka & Yamada, 1978) and both drug actions can be blocked by theophylline (Sawynok & Jhamandas, 1976). Conversely, dipyridamole, an inhibitor of the adenosine uptake (Huang & Daly, 1974) potentiates the inhibition of transmitter release by both adenosine and morphine (Gintzler & Musacchio 1975;Hayashi et al, 1978). In addition, methylxanthine derivatives, thought to act as phosphodiesterase inhibitors, can both potentiate morphine withdrawal symptoms and induce a quasi-morphine withdrawal syndrome in naive or 0007-1188/80/050131-07 $01.00 morphine-dependent rats (Francis, Roy & Collier, 1975;Butt, Collier, Cuthbert, Francis & Saeed, 1979).…”