EFFECTS OF ADENOSINE 5′‐TRIPHOSPHATE (ATP) AND Β‐γ‐METHYLENE ATP ON THE RAT URINARY BLADDER

1 The nerve-evoked contractions elicited by transmural electrical stimulation of mouse urinary bladders superfused in modified Krebs Ringer buffer containing 1 IAM atropine plus 3.4 IBM guanethidine were inhibited by adenosine (ADO) and related nucleoside analogues with the following rank order of potency: R-phenylisopropyladenosine (R-PIA) > cyclohexyladenosine (CHA) > 5'N-ethylcarboxamido adenosine (NECA) > ADO > S-phenylisopropyladenosine (S-PIA). Tissue preincubation with 8-phenyltheophylline (8-PT) displaced to the right, in a parallel fashion, the NECA concentration-response curve.2 The contractions elicited by application of exogenous adenosine 5'-triphosphate (ATP) were also inhibited by ADO and related structural analogues. The rank order of potency to reduce the motor response to ATP was: NECA > 2-chloroadenosine (CADO) > R-PIA > ADO > CHA > S-PIA. 3 The ADO-induced ATP antagonism was of a non-competitive nature and was not specific. Tissue incubation with 10 AM NECA not only reduced the motor responses elicited by ATP, but also 5-hydroxytryptamine, acetylcholine and prostaglandin F2CK. The action of NECA was antagonized following tissue preincubation with 8-PT. The inhibitory action of NECA was not mimicked by 10 gM CHA. 4 The maximal bladder ATP contractile response was significantly increased by tissue preincubation with 5-30 gM 8-PT. 5 The 0.15 Hz evoked muscular twitch was significantly increased by 8-PT while dipyridamole consistently reduced the magnitude of the twitch response. These results are consonant with the hypothesis that an endogenous ADO tone modulates the bladder neurotransmission. 6 A working model is proposed suggesting the presence of ADO-Al and A2 receptors in the mouse urinary bladder. The A1 receptor subpopulation is probably of presynaptic origin whereas the smooth muscle membranes contain a population of the A2 receptor subtype.

Section: Discussionmentioning

confidence: 81%

Pharmacological characterization of adenosine A₁ and A₂ receptors in the bladder: evidence for a modulatory adenosine tone regulating non‐adrenergic non‐cholinergic neurotransmission

Acevedo

Contreras

Escalona

et al. 1992

“…Similar studies of purine nucleotide potencies have been carried out in a number of other tissues and a comparative agonist potency order has been demonstrated (see . In the guinea-pig vas deferens (Fedan et al, 1982;Burnstock et al, 1983;, the rat and guinea-pig urinary bladder (Brown et al, 1979;Burnstock et al, 1983), the perfused pancreas vascular bed (Chapal & Loubatieres-Mariani, 1983), the rat aorta and femoral artery White et al, 1985) and the rabbit ear artery (Kennedy & Burnstock, 1985a), P2-purinoceptors mediate contraction. A rank potency order of a,fi-methylene, 0,ymethylene ATP > ATP = 2-methylthio ATP is indicated in these tissues.…”

Section: Pharmacologymentioning

confidence: 99%

P₂‐purinoceptors of two subtypes in the rabbit mesenteric artery: reactive blue 2 selectively inhibits responses mediated via the P_2y‐ but not the P_2x‐purinoceptor

Burnstock

Warland

1987

234

146

I mc-Methylene ATP and ATP both produced concentration-dependent contractions of the isolated mesenteric artery of the rabbit that were not inhibited by reactive blue 2. 2 In preparations where the tone had been raised with noradrenaline, ATP and 2-methylthio ATP, but not a,-methylene ATP, produced relaxations of the vessel. These relaxations were inhibited in the presence of reactive blue 2. 3 Reactive blue 2 did not inhibit the contractions to noradrenaline, and only slightly inhibited relaxations to adenosine and acetylcholine.4 The rank order of potency of purine nucleotide analogues in contracting the vessel was: a,-methylene ATP > P,'y-methylene ATP = 2-methylthio ATP > ATP, and in relaxing the vessel at raised tone was: 2-methylthio ATP > ATP > ,y-methylene ATP > a,-methylene ATP.5 It is concluded from this study that in the isolated mesenteric artery ofthe rabbit, purine nucleotides act via P2y-purinoceptors to cause the muscle to relax and via P2x-purinoceptors to cause the muscle to contract. The results also suggest that reactive blue 2 selectively inhibits responses mediated via the P2y-purinoceptor, at least within a limited concentration range.

“…ATP produces a rapidly developing phasic bladder contraction and is considered a likely noncholinergic excitatory transmitter at this level (Brown et al, 1979;Bo & Burnstock, 1990;Brading & Williams, 1990;Luheshi & Zar, 1990). After the early suggestion of Holton & Holton (1954) and Holton (1959), a role for ATP as a sensory transmitter has been recently reconsidered (Jahr & Jessell, 1983;Fyffe & Perl, 1984).…”

Section: Introductionmentioning

confidence: 99%

Tachykinin antagonists and capsaicin‐induced contraction of the rat isolated urinary bladder: evidence for tachykinin‐mediated cotransmission

Maggi

Patacchini

Santicioli

et al. 1991

1 The possible involvement of tachykinins (TKs) in the contraction produced by capsaicin in the rat isolated urinary bladder was addressed on the hypothesis that co-release of substance P (SP) and neurokinin A (NKA) occurs from sensory nerve terminals. 2 A low concentration of SP (30 nM) produced a rapid contraction which faded to baseline within 10min. A low concentration of NKA (10nM) produced a slowly developing contraction which was still evident at 10min. Capsaicin (1 pM) produced a rapid phasic response and a tonic response (late response to capsaicin). Co-administration of SP and NKA mimicked the response to capsaicin more than each TK alone. 3 Fading of the response to SP was not caused by receptor desensitization and was partially prevented by peptidase inhibitors.4 Spantide (3pM) selectively antagonized the SP-induced contraction while L-659,877 (3-lOpM) or MEN 10,376 (10-30pM) which are NK2 receptor selective antagonists selectively blocked the response to NKA.Co-administration of spantide and L-659,877 inhibited the response to both SP and NKA by an amount not greater than that produced by each antagonist alone. 5 Spantide selectively reduced the peak response to capsaicin, while leaving the late response unaffected.L-659,877 (3 pM) and MEN 10,376 (10pM) selectively inhibited the late response to capsaicin while, at higher concentrations, also reduced the peak response to capsaicin. Co-administration of spantide and L-659,877 reduced the peak response to capsaicin more than that produced by each antagonist alone. 6 Bombesin (10nM) produced a tonic contraction similar to that induced by NKA. The response to bombesin was not affected by spantide, L-659,877 or MEN 10,376. 7 P2. purinoceptor desensitization by repeated administration of a,fl-methylene ATP depressed the twitch response to electrical stimulation of postganglionic nerves but did not affect the peak or the late response to capsaicin. 8 We conclude that multiple TKs are coreleased by capsaicin in the rat bladder and mediate the capsaicin-induced contraction by activating both NKI and NK2 receptors. Endogenous TK with preferential affinity for the NK, receptor (putatively SP) are selectively involved in the peak response to capsaicin while endogenous TK with preferential affinity for the NK2 receptor (putatively NKA) are selectively involved in the late response to capsaicin and partly contribute to the peak response. These findings provide pharmacological evidence for tachykinin-mediated cotransmission in the rat urinary bladder. ATP is unlikely to be involved in the efferent function of capsaicin-sensitive sensory nerves in the rat bladder.