Characterization of adenosine receptors in rat brain by (?)[3H]N6-phenylisopropyladenosine

1 The effects of tienoxolol, (ethyl 2-[3-[(1,1-dimethylethyl)amino]-2-hydroxypropoxy]-5-[(2-thienylcarbonyl) amino] benzoate, hydrochloride), a novel drug exhibiting both diuretic and Padrenoceptor blocking properties, were investigated on urinary 6-keto-prostaglandin Fl, (6-keto-PGFI,) and PGE2 excretion in the rat and compared to those of reference diuretic (furosemide) and Padrenoceptor antagonists (acebutolol, propranolol). Since tienoxolol was shown to bind to A, and A2 adenosine receptors, the action of theophylline was also evaluated.2 Tienoxolol (8-128mgkg-', p.o.) induced a dose-related increase of 6-keto-PGFI, excretion from 32 mg kg-' but a significant elevation of urinary PGE2 levels was only reached after administration of 128 mg kg-'. However, renal prostaglandin concentrations were not modified by tienoxolol.3 Furosemide (32 mg kg-') displayed a strong diuretic activity but did not enhance 6-keto-PGFI,, excretion. Likewise, the latter was unaffected by acebutolol and propranolol (128 mg kg-') and no significant diuresis was observed following administration of these two P-blocking agents. Theophylline (64 mg kg-1), like tienoxolol, was able to induce both diuresis and urinary prostaglandin excretion. Furthermore, they bound with similar affinities to A, and A2 adenosine receptors. This led to the suggestion that a relationship between P,-purinoceptors, prostaglandin release, diuresis and natriuresis could exist.4 Oral co-administration of NECA (0.2 mg kg-') with tienoxolol markedly reduced the urinary 6-keto-PGF,c, excretion observed when tienoxolol was administered alone. However, neither diuresis nor natriuresis were modified, demonstrating that the proposed relationship was untenable. 5 In conclusion, PGI2 probably does not participate in the diuretic and natriuretic activity of tienoxolol. The increase of urinary 6-keto-PGF,g excretion may result not only from the haemodynamic properties of the drug but also from the rise of the urinary flow induced by tienoxolol.

Section: Preparation Of Brain Membranes For Adenosine Binding Assaysmentioning

confidence: 99%

Section: Radioligand Binding Assaysmentioning

confidence: 99%

Effect of tienoxolol, a new diuretic β‐blocking agent, on urinary prostaglandin excretion in the rat

Caussade¹,

Cloarec²

1993

“…The slices were preincubated and labelled as described previously (Fredholm et al 1982). All (Bruns et al, 1980;Schwabe & Trost, 1980). Three different preparations of pooled cat cortical membranes were used in these studies.…”

Section: Formation Of [3hi-cyclic Ampmentioning

confidence: 99%

Treatment with N‐ethylmaleimide selectively reduces adenosine receptor‐mediated decreases in cyclic AMP accumulation in rat hippocampal slices

Fredholm

Lindgren

Lindström

1985

“…Quantitative investigations of the A1 adenosine receptor have in the main been limited to applying radioligand binding assays using either agonists (e.g. [3H]-R-PIA: Schwabe & Trost, 1980) Lohse et al, 1987). Studies of adenylyl cyclase activity in cell-free preparations from the CNS have also been carried out to investigate A1 adenosine I Author for correspondence.…”

Section: Introductionmentioning

confidence: 99%

A₁ adenosine receptor inhibition of cyclic AMP formation and radioligand binding in the guinea‐pig cerebral cortex

Alexander¹,

Curtis²,

Kendall³

et al. 1994