Some Effects of Dipyridamole, Hexobendine and Lidoflazine on Inhibitory Processes in Rabbit Duodenum

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.

Section: Discussionmentioning

confidence: 99%

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

Coleman¹

1976

“…In the present preparation, however, dipyridamole was not found to be effective in either potentiating the inhibitory responses induced by TMS or in causing any consistent effect on the ATP-induced responses. The ineffectiveness of dipyridamole in enhancing the relaxations resulting from the excitation of nonadrenergic inhibitory nerves in the rabbit duodenum (Hulme & Weston, 1974) and in the rat stomach (Heazell, 1975) has also been reported.…”

Section: Inhibitory Pathwaymentioning

confidence: 99%

Dissimilarity Between the Responses to Adenosine Triphosphate or Its Related Compounds and Non‐adrenergic Inhibitory Nerve Stimulation in the Longitudinal Smooth Muscle of Pig Stomach

Ohga

Taneike

1977

1 Transmural electrical stimulation (TMS) of longitudinal smooth muscle strips taken from the cardiac portion of the pig stomach produced biphasic responses consisting of initial contractions followed by relaxations. The excitatory component was enhanced by neostigmine and abolished by atropine. After atropine treatment, TMS and nicotine or 1,1-dimethyl-4-phenyl-piperazinium, caused a relaxation or a relaxation followed by an after-contraction. All of these responses were abolished or reduced reversibly with tetrodotoxin and cocaine, while hexamethonium only abolished the response to ganglion-stimulating agents. 2 The relaxation caused by TMS reached a maximum amplitude at 5-10 Hz, and was entirely resistant to the effects of a-and P-adrenoceptor blocking agents, or a combination of them, and also to guanethidine. These results strongly suggested that the relaxation was elicited by stimulation of intramural non-adrenergic inhibitory neurones. 4 Stimulation of the intramural inhibitory neurones of the tissue consistently evoked an inhibitory junction potential, which showed a summation during repetitive stimulation. One the other hand, ATP elicited mainly a small depolarization of a few mV. 5 When the desensitization to ATP of the muscle was achieved in the presence of atropine and guanethidine, the relaxation induced by stimulation of the non-adrenergic inhibitory neurones could be evoked without any modification. 6 Dipyridamole neither potentiated the inhibitory responses due to stimulation of the intramural inhibitory neurones nor showed any consistent effect on the ATP-induced response. 7 From these results, it is unlikely that ATP, or any related compound, is the transmitter substance of the intramural inhibitory neurones in the longitudinal smooth muscle of the pig stomach.

“…Stafford (1966) reported that the effects of adenosine in rabbit intestine were potentiated by dipyridamole and Satchell, Lynch, Bourke & Burnstock (1972) have claimed that the effects of adenosine, ATP and of intramural stimulation in guinea-pig taenia coli are potentiated by dipyridamole and by hexobendine. However, we have failed to confirm potentiation of the effects of adenosine, ATP and intramural stimulation in the presence of dipyridamole, hexobendine and lidoflazine, and consider that the data presented by Stafford (1966) and by Satchell et al ( 1972) were inadequate to allow the claim that potentiation of inhibitory responses had occurred (Hulme & Weston, 1974).…”

Section: Introductionmentioning

confidence: 79%

“…In view of this and of the disparity between the work of Stafford (1966) and Satchell et al (1972) and that of Hulme & Weston (1974), it was decided to determine the characteristics of adenosine accumulation in rabbit intestine. In addition, the effects of dipyridamole, hexobendine and lidoflazine were examined to discover whether these compounds affected adenosine uptake itself and/or the subsequent metabolism of adenosine within the tissue.…”

Section: Introductionmentioning

confidence: 99%

“…Close examination of the work of Kraupp et al (1966), Afonso et al (1968, Kolassa et al (1970), and Hopkins & Goldie (1971), reveals that these workers have not shown that an adenosine uptake process exists (see Iversen, 1970) but merely that tissues accumulate radioactivity following exposure to [ 3HI -adenosine. In view of this and of the disparity between the work of Stafford (1966) and Satchell et al (1972) and that of Hulme & Weston (1974), it was decided to determine the characteristics of adenosine accumulation in rabbit intestine. In addition, the effects of dipyridamole, hexobendine and lidoflazine were examined to discover whether these compounds affected adenosine uptake itself and/or the subsequent metabolism of adenosine within the tissue.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The Accumulation of Adenosine in Rabbit Intestinal Muscle

Hulme

Weston

1974

Self Cite

Strips of longitudinal muscle from rabbit intestine accumulated radioactivity when exposed to [3H]‐adenosine. Accumulation of radioactivity was not sodium‐dependent or ouabain‐sensitive, but was reduced by cooling, zero glucose plus bubbling with N2, 2,4, dinitrophenol, dipyridamole, hexobendine and lidoflazine. After 7 min exposure to [3H]‐adenosine, the tissue was found to contain radioactive adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP) and adenosine itself in the approximate ratio 13: 6: 4: 1. In the presence of dipyridamole, hexobendine or lidoflazine (each 1 μm), the amounts of radioactive ATP, ADP, AMP and adenosine were reduced with the concentration of adenosine not significantly different from controls. It is concluded that energy‐dependent uptake of adenosine does not occur in the longitudinal muscle of rabbit intestine. Adenosine enters the tissue by a passive process and rapidly becomes phosphorylated giving rise to apparently high tissue: medium ratios. The drugs dipyridamole, hexobendine and lidoflazine appear to reduce the accumulation of radioactivity by preventing the formation of adenosine phosphate derivatives.