Molecular identification and pharmacological characterization of adenosine receptors in the guinea-pig colon.
The aim of this study is to elucidate the role of adenosine in the motor function of the guinea-pig distal colon.2 To determine whether adenosine A(1) receptors and A(2B) receptors are expressed in the guinea-pig colon, we employed the reverse transcription-polymerase chain reaction (RT - PCR). The gene expression of A(1) receptor and A(2B) receptor was found for the first time in the guinea-pig proximal and distal colon.3 Adenosine A(1) agonist N(6)-cyclopentyladenosine (CPA), and A(1)/A(2) agonist 5'-N-ethylcarboxamidoadenosine (NECA) concentration-dependently inhibited neurogenic responses to electrical field stimulation (EC(50)=1.07x10(-8) and 2.12x10(-8) M) in the longitudinal muscle, but A(2A) agonist 2-p-(2-carboxyethyl)phenylethylamino-5'-N-ethycarboxamido-ad enosine (CGS21680) had only a slight inhibitory effect (25.9%, 1 microM). A(1) antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 10 nM: A(1) selective concentration) antagonized responses to CPA and NECA. Furthermore, the affinity order of antagonists at inhibiting the effect NECA was: DPCPX>8-phenyltheophylline (8-PT: A(1)/A(2) antagonist).3 In the presence of tetrodotoxin (TTX, 0.3 microM), CPA and NECA relaxed myogenic precontraction induced by KCl (50 mM) (EC(50)=1.26x10(-5) and 1.04x10(-5) M, respectively), but CGS21680 (1 microM) did not cause any relaxation. DPCPX did not affect responses to CPA and NECA at a concentration of 10 nM, but a higher concentration (1 microM) of DPCPX and 10 microM of 8-PT antagonized those responses.5 These data lead us to the hypothesis that adenosine may mediate relaxation through two different inhibitory receptor subtypes; A(1) receptors on the enteric neuron and A(2B) receptor on the smooth muscle in the guinea-pig distal colon.
Kadowaki
M
M
Pharmacological Research Laboratory, Fujisawa Pharmaceutical Co. Ltd., Osaka 532-0031, Japan.
Takeda
M
M
Tokita
K
K
Hanaoka
K
K
Tomoi
M
M
D000109:Acetylcholine / Q000494:pharmacology; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide) / Q000494:pharmacology; D000818:Animals; D003106:Colon / Q000187:drug effects*; D004558:Electric Stimulation; D005769:Gastrointestinal Motility / Q000187:drug effects; D006168:Guinea Pigs; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D010627:Phenethylamines / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D012333:RNA, Messenger / Q000096:biosynthesis; D043704:Receptor, Adenosine A2B; D018047:Receptors, Purinergic P1 / Q000096:biosynthesis / Q000187:drug effects*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014665:Vasodilator Agents / Q000494:pharmacology
D010627:Phenethylamines; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D012333:RNA, Messenger; D043704:Receptor, Adenosine A2B; D018047:Receptors, Purinergic P1; D014665:Vasodilator Agents; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D019830:Adenosine-5'-(N-ethylcarboxamide); C048599:N(6)-cyclopentyladenosine; D011189:Potassium Chloride; D000241:Adenosine; D000109:Acetylcholine