Cross talk between receptors mediating contraction and relaxation in the arterioles but not the dilator muscle of the rat iris.
1. Sympathetic nerve stimulation causes contraction of the dilator muscle and the large arterioles of the iris via the activation of alpha 1B-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. 2. Increasing intracellular cyclic AMP with dibutyryl cyclic AMP (1 mM), forskolin (50 microM) or isobutylmethylxanthine (100 microM) 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. 3. 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. 4. The beta-adrenoceptor agonist, isoprenaline (1 microM), the adenosine-A1,-A2 agonist, N-ethylcarboxamidoadenosine NECA (100 nM), in the presence of the A1-selective antagonist, 8-cyclopentyl-1, 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 microM) 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. beta-adrenoceptor, adenosine-A2 and CGRP, but only 1 Gs-linked receptor, i.e. beta-adrenoceptors, on the dilator muscle cells.2+ '
Division of Neuroscience, John Curtin School of Medical Research, Australian National University, Canberra.
D J
DJ
Gould
M
M
Vidovic
C E
CE
Hill
D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D001483:Base Sequence; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism; D066298:In Vitro Techniques; D007498:Iris / Q000098:blood supply*; D008297:Male; D008969:Molecular Sequence Data; D009119:Muscle Contraction / Q000502:physiology; D009126:Muscle Relaxation / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D009475:Neurons, Afferent / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects / Q000502:physiology*; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000187:drug effects / Q000378:metabolism; D018047:Receptors, Purinergic P1 / Q000187:drug effects
D012333:RNA, Messenger; D018340:Receptors, Adrenergic, alpha-1; D018015:Receptors, Calcitonin Gene-Related Peptide; D018047:Receptors, Purinergic P1; D000242:Cyclic AMP; D012194:RNA-Directed DNA Polymerase; D019204:GTP-Binding Proteins