EVIDENCE FOR THE PRESENCE OF A1 AND A2 ADENOSINE RECEPTORS IN THE VENTRAL AORTA OF THE DOGFISH SHARK, SQUALUS-ACANTHIAS

Isolated, endothelium-free rings of vascular smooth muscle (VSM) from the ventral aorta of the dogfish shark, Squalus acanthias, were used to examine the vasoactive effects of various adenosine agonists. Cumulative addition of 2-chloroadenosine (2 Cl-ADO) over the concentration range 10 nM - 1 mM resulted in a biphasic response, with a significant increase in tension at 1-mu-M and a more significant decline in tension at 100-mu-M and 1 mM, suggesting that this tissue may possess both A1 and A2 adenosine receptors. N6-Cyclopentyladenosine (N-6 CPA) and N6-(2-phenylisopropyl)adenosine, R(-)isomer (R-PIA), generally considered to be more A1 specific, also produced slight, but significant increases in tension, but only at relatively high concentrations. The more specific A1 agonist, N6-(25)-[2-endo-norbonyl] adenosine [(S)-ENBA] produced a significant increase in tension at 1 pM, reaching 28% above control at 10 nM. The response to (S)-ENBA was also biphasic, with a fall in tension at 10-mu-M. The relatively non-specific agonist 5'-N-ethylcarboxamidoadenosine (NECA) produced a small, but significant, increase in tension at 1-mu-M, with no subsequent decline in tension at higher concentrations. These results allow us to assign a tentative structure-activity relationship (SAR) for an increase in tension of (S)-ENBA much greater than R-PIA greater-than-or-equal-to 2-Cl ADO = N-6 CPA = NECA; for the decrease, the SAR is (S)-ENBA > 2-Cl ADO > R-PIA > N-6 CPA = NECA. These SARs are consistent with the hypothesis that the VSM from the ventral aorta of this elasmobranch fish contains both A1 and A2 adenosine receptors. This is the first such description of both adenosine receptors in fish VSM. The role of a putative release of adenosine from the fish heart on branchial hemodynamics remains to be determined.