Cross talk between receptors mediating contraction and relaxation in the arterioles but not the dilator muscle of the rat iris
Authors: Gould D.J. , Vidovic M. , Hill C.E. 
Published: July 2012

Sympathetic nerve stimulation causes contraction of the dilator muscle and the large arterioles of the iris via the activation of α1B‐adrenoceptors. We have investigated whether increases in adenosine 3′: 5′‐cyclic monophosphate (cyclic AMP) and the activation of receptors in these tissues can modulate these nerve‐mediated contractions.
0Increasing intracellular cyclic AMP with dibutyryl cyclic AMP (1 mM), forskolin (50 μm) or isobutylmethylxanthine (100 μm) produced relaxation of both the dilator and the arterioles, abolished the nerve‐mediated constriction of the arterioles, but potentiated the nerve‐mediated contraction of the iris dilator.
Pretreatment of the preparations with cholera toxin, to activate Gs permanently, caused a dilatation of the arterioles and abolished the nerve‐mediated constriction but had no effect on the dilator muscle.
The β‐adrenoceptor agonist, isoprenaline (1 μm), the adenosine‐A1,‐A2 agonist, N‐ethylcarboxami‐doadenosine NECA (100 nM), in the presence of the A1selective antagonist, 8‐cyclopentyl‐l, 3‐dipropylxanthine (DPCPX, 10 nM), and calcitonin gene‐related peptide (CGRP, 10 nM) all separately caused a dilatation of the arterioles and abolished the nerve‐mediated constriction, while only isoprenaline (1 μm) produced an effect on the dilator, i.e. a relaxation but a potentiation of the nerve‐mediated contraction. These results suggest the presence of at least 3 types of receptor linked to Gs and an increase in cyclic AMP in the arterioles, i.e. β‐adrenoceptor, adenosine‐A2 and CGRP, but only 1 Gs‐linked receptor, i.e. β‐adrenoceptors, on the dilator muscle cells.
Neither the A1‐selective agonist, cyclohexyladenosine (CHA, 10 nM) nor the A1‐selective antagonist, DPCPX (10 nM) had any significant effect on the nerve‐mediated constriction of the arterioles, suggesting that presynaptic A1‐receptors do not play a role in modulating the sympathetic nerve‐mediated constriction.
Forskolin (50 μm), in the presence of capsaicin (10 μm) to inactivate unmyelinated CGRP‐containing sensory nerves, still caused a dilatation of the arterioles and abolished nerve‐mediated constriction suggesting that the effects on the blood vessels were due to increases in cyclic AMP in the arteriolar cells and not in the sensory nerves.
Using reverse transcription polymerase chain reaction, we have demonstrated expression of the α1B and α1c molecular subtypes in the tissues of the iris. These molecular subtypes most likely correspond to the α1B and α1A pharmacological subtypes, respectively.
Preincubation in NG‐nitro‐L‐arginine methyl ester (L‐NAME, 10 μm), but not D‐NAME (10 μm), reduced the efficacy of forskolin in inhibiting the sympathetic nerve‐mediated vasoconstriction. These results suggest that the inhibition of sympathetic nerve‐mediated constriction by cyclic AMP in the arterioles is indirect via the production of nitric oxide.
Our results demonstrate that there is ‘cross talk’ between receptors linked to increases in cyclic AMP and α1B‐adrenoceptors in the arterioles of the rat iris, but that no such interaction occurs between cyclic AMP and α1B‐adrenoceptors in the dilator muscle. The interaction in the arterioles occurs as a result of cyclic AMP‐mediated stimulation of nitric oxide synthesis, presumably by the arteriolar endothelial cells.