title: An in vivo model for dissociating alpha 2-and DA2-adrenoceptor activity in an ocular adnexa: utility of the cat nictitating membrane preparation.
abstract: Recent reports from this laboratory indicate that dopamine (DA2) agonists can lower intraocular pressure (IOP) in rabbits, monkeys and rats. This communication suggests that the cat nictitating membrane (CNM) preparation is a useful model for localizing the site(s) and mechanism(s) of action of dopamine (DA2) agonists and that this model can be used to discriminate between alpha 2 and DA2 activity. This in vivo preparation consists of indirect (neuronal)- and direct (agonist)-induced activation of the CNM by: 1) pre- and postganglionic stimulation of sympathetic nerves and 2) injection of norepinephrine (NEPI) into the external carotid artery (i.a.). A variety of DA2-agonists (ergolines, azepines, aminotetralins, aporphines) can cause dose-dependent depression of neuronally mediated contractions with minimal effects on contractions elicited by NEPI i.a. Characteristically, DA2-agonists depressed contractions elicited by low frequency (2 & 4 Hz) stimulation more than high frequency (6 & 8 Hz) stimulation. For example, the inhibitory effects of an ergoline derivative LY141865 on neuronally mediated contractions of the CNM could be reversed (or prevented) by relatively selective DA2 antagonists, such as sulpiride and domperidone, but not by relatively selective alpha 2-antagonists, such as yohimbine and rauwolscine. Interestingly, alpha 2-adrenoceptor agonists, such as clonidine and xylazine, caused less depression of nerve-stimulated responses than did DA2-agonists at the same dose. This modest suppression by alpha 2-agonists could be inhibited by yohimbine but not by sulpiride or domperidone. These results with the CNM document the presence of DA2 receptors on sympathetic neurons innervating an ocular adnexa and demonstrate a model for dissociating DA2 from alpha 2 activity.
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D002415:Cats; D004873:Ergolines / Q000494:pharmacology; D005260:Female; D008297:Male; D008954:Models, Biological; D009119:Muscle Contraction / Q000187:drug effects; D009474:Neurons / Q000378:metabolism; D009541:Nictitating Membrane / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*; D019257:Quinpirole; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000316:Adrenergic alpha-Agonists; D004873:Ergolines; D011942:Receptors, Adrenergic, alpha; D011954:Receptors, Dopamine; D019257:Quinpirole