A(2A) adenosine receptor mediated potassium channel activation in rat epididymal smooth muscle

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Abstract

1. The effects of A2 adenosine receptor agonists upon phenylephrine-stimulated contractility in preparations of rat epididymis were investigated. 2. Preparations responded to phenylephrine (3 μM) with submaximal contractions. Adenosine and the stable agonists 5'-N-ethylcarboxamido-adenosine (NECA) and 2-p-(2-carboxyethyl) phenethylamino-N-ethylcarboxamide adenosine (CGS 21680) inhibited phenylephrine-induced contractions (potency order, NECA > CGS 21680 > adenosine). The A(2A) receptor-selective antagonist, 4-(2-[7-amino-2-(2-furyl)[1,2,4]-triazolo-[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol (ZM 241385, 30 μM) blocked the response to NECA. 3. The A(2A) adenosine receptor-mediated inhibitory responses to NECA were reduced by the K(ATP) channel blocker, glibenclamide (3 μM) and abolished by charybdotoxin (100 nM). 4. The diterpene forskolin elicited a concentration-dependent inhibition of phenylephrine (3 μM)-stimulated contractility (by 62 ± 8% of control at 100 μM). Charybdotoxin (100 nM), but not glibenclamide (3 μM) blocked the forskolin (10 μM) inhibition of phenylephrine-stimulated glibenclamide contractility. 5. NECA elicited concentration-dependent increases in both cyclic AMP and cyclic GMP accumulation which were antagonized by ZM 241385 (30 nM). 6. The protein kinase G activator, APT-cyclic GMP (8-(-Aminophenylthio) guanosine-3',5'-cyclic monophosphate) and the protein kinase A activator (Sp)-8-bromoadenosine-3',5'-cyclic monophosphorothioate (Sp-8-Br-cyclic AMPs), inhibited phenylephrine (3 μM) induced contractions of rat epididymis. Glibenclamide (3 μM), but not charybdotoxin (100 nM), inhibited ATP-cyclic GMP responses. Charybdotoxin (100 nM), but not glibenclamide (3 μM) reduced the effect of Sp-8-Br-cyclic AMPs. 7. This study shows that the A(2A) adenosine receptor inhibition of epididymal contractility may be mediated through the activation of charybdotoxin- and glibenclamide-sensitive potassium channels and may involve the activation of both protein kinases A and G.

Original languageEnglish
Pages (from-to)685-691
Number of pages7
JournalBritish Journal of Pharmacology
Volume130
Issue number3
DOIs
Publication statusPublished - 1 Jan 2000
Externally publishedYes

Keywords

  • A(2A) adenosine receptor
  • Cyclic GMP
  • K(ATP) channels
  • Protein kinase G
  • Rat epididymis

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