Alpha-2 adrenergic modulation of norepinephrine secretion in the perfused rabbit iris-ciliary body.
Clonidine and other selective alpha-2 adrenergic agonists have been found to lower intraocular pressure in the eyes of rabbits and primates, including humans. It has been suggested that the ocular hypotensive response to alpha-2 agonists may be mediated, in part, by prejunctional inhibition of norepinephrine secretion at intraocular synapses. In this study, we have investigated the effects of adrenergic agonists and antagonists on field-stimulated, Ca++-dependent release of 3H-norepinephrine (3H-NE) from isolated, perfused rabbit iris-ciliary bodies and have utilized radioligand binding methods to identify prejunctional adrenoceptors in this tissue. Clonidine (10(-9)-10(-5) M) produced a dosage-dependent inhibition of stimulation-evoked 3H-NE secretion (EC50 approximately equal to 3 X 10(-8) M), but did not alter basal secretion. Other adrenergic agonists capable of activating alpha-2 adrenoceptors (e.g., epinephrine, norepinephrine and xylazine) also significantly depressed 3H-NE secretion, whereas selective alpha-1 adrenergic or beta adrenergic agonists were without effect. Clonidine-mediated inhibition of 3H-NE release was reversed by the selective alpha-2 antagonist yohimbine (10(-7) M), but was unaffected by prazosin or timolol. Yohimbine alone markedly enhanced 3H-NE secretion, indicating tonic activation of prejunctional alpha-2 adrenoceptors by endogenous released norepinephrine. Forskolin or 8-bromo-cAMP, which alone enhanced norepinephrine secretion, failed to attenuate the inhibitory responses to alpha-2 agonists. 3H-rauwolscine binding measurements showed a small decrease in alpha-2 receptor sites in iris-ciliary body membranes following surgical sympathetic denervation. It is concluded that the rabbit iris-ciliary body contains functional, prejunctional alpha-2 adrenoceptors which may play an autoregulatory role in vivo and contribute to the ocular effects of adrenergic drugs.
D000818:Animals; D002924:Ciliary Body / Q000378:metabolism*; D000242:Cyclic AMP / Q000502:physiology; D003714:Denervation; D004558:Electric Stimulation; D066298:In Vitro Techniques; D007498:Iris / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D010477:Perfusion; D011817:Rabbits; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D013566:Sympathomimetics / Q000494:pharmacology; D015016:Yohimbine / Q000378:metabolism
D011942:Receptors, Adrenergic, alpha; D013566:Sympathomimetics; D015016:Yohimbine; D000242:Cyclic AMP; D009638:Norepinephrine