Intestinal arteriolar responses to mucosal and serosal applications of adenosine analogues.
Adenosine or its synthetic analogues were topically applied to the intestinal jejunum while steady-state blood flow was calculated in submucosal arterioles using video microscopy. Blood flow increased (220 or 130% of control) with the serosal application of 10(-6) M N-ethyl carboxamido adenosine (NECA, A2-selective agonist) or 2-chloro adenosine (2CA, nonselective agonist) but not with cyclohexyl adenosine (CHA, A1-selective agonist). The nonselective competitive antagonist, 8-phenyl theophylline, attenuated the response evoked by NECA. The mucosal application of 10(-6) M CHA caused blood flow decreases (81% of control), but neither NECA nor 2CA evoked a response. These observations suggest a mucosal diffusion barrier, so the concentrations of the analogues were raised one hundredfold. Serosal 10(-4) M CHA or NECA caused blood flow increases, but the effects were negligible with mucosal application, suggesting that the mucosa was indeed impermeable to these compounds. The responses evoked by 10(-4) M 2CA were similar on the serosa or mucosa (200-220% of control), submaximal (maximum = 400% of control at 10(-3) M), and not antagonized by 8-phenyl theophylline or by the cellular uptake inhibitor, nitrobenzyl-6-thio guanosine. In context with earlier studies, greater than 10(-6) M 2CA probably evokes vasodilation that is not entirely mediated by extracellular receptors. Serosal adenosine (10(-4) M) caused submaximal blood flow increases (200% of control) that were not potentiated by nitrobenzyl-6-thio guanosine or another transport inhibitor, dipyridamole.(ABSTRACT TRUNCATED AT 250 WORDS)
D015762:2-Chloroadenosine; D000241:Adenosine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology*; D019830:Adenosine-5'-(N-ethylcarboxamide); D000287:Administration, Topical; D000818:Animals; D006439:Hemodynamics / Q000187:drug effects; D007413:Intestinal Mucosa / Q000098:blood supply* / Q000187:drug effects; D007583:Jejunum / Q000098:blood supply* / Q000187:drug effects; D008297:Male; D008833:Microcirculation / Q000187:drug effects*; D008853:Microscopy / Q000379:methods; D051381:Rats; D011919:Rats, Inbred Strains; D011983:Receptors, Purinergic / Q000187:drug effects / Q000502:physiology; D012704:Serous Membrane / Q000098:blood supply* / Q000187:drug effects; D014741:Video Recording
D011983:Receptors, Purinergic; D015762:2-Chloroadenosine; D019830:Adenosine-5'-(N-ethylcarboxamide); D000241:Adenosine