Naphazoline-induced neuroendocrine changes: increases in ANP and cGMP levels, but suppression of NE, 3H-NE, and cAMP levels in rabbit eyes.

The objective of this study was to determine whether naphazoline, an alpha 2 (alpha2)/imidazoline (I1) agonist, can alter endogenous levels of atrial natriuretic peptide (ANP) and norepinephrine (NE) in aqueous humor and cyclic nucleotide (cAMP, cGMP) accumulation and NE overflow in the iris-ciliary body (ICB) of the rabbit eye. Topical naphazoline (25, 75, and 250 microg) caused a dose-dependent elevation of the ANP levels (36, 54, and 137 pg/ml, respectively) in aqueous humor. This effect was antagonized by pretreatment with efaroxan, an antagonist of I1/alpha2 receptors. Another alpha2/I1 agonist, moxonidine (75 microg topically), caused significant increases in ANP levels in aqueous humor, whereas other relatively selective alpha2-adrenergic receptor agonists, brimonidine (50 microg topically) and oxymetazoline (75 microg topically), did not. In naphazoline (75 microg) pretreated eyes, the NE levels in aqueous humor were attenuated by 36% (from 6.0 to 3.8 pg/ml). Furthermore, naphazoline (1, 10, and 100 micromol/l) caused a dose-related inhibition of NE release from ICBs: 25, 45, and 80%, respectively. The isoproterenol (1 micromol/l) stimulated cAMP accumulation was inhibited 53% by naphazoline (100 micromol/l). In contrast, naphazoline significantly increased the cGMP levels in ICBs. These data demonstrate that naphazoline acts on I1 receptors to increase ANP and to reduce NE levels in aqueous humor. The former effect could also contribute to elevation of cGMP levels and inhibition of cAMP accumulation in the ICB. Further studies will be required to determine if elevation of ANP levels is a critical component of naphazoline-induced alteration of aqueous humor dynamics.

Pharmacological evidence of a role for prejunctional imidazoline (I(1)) receptors in ocular function.

Imidazoline and guanidiniun-substituted isoindoline compounds have been reported to demonstrate affinity for the putative imidazoline receptors (I(1)) and alpha-2 (alpha(2)) adrenoceptors. The purpose of this study was to determine the relative contribution of I(1) receptors to ocular actions of moxonidine (MOX) and brimonidine (BRIM) by utilizing relatively selective alpha(2) and I(1) antagonists. MOX, an alpha(2)/I(1) receptor agonist, BRIM, a selective alpha( 2) agonist, efaroxan (EFA), an I(1)/alpha(2) antagonist and rauwolscine (RAU), a relatively selective alpha(2) antagonist, were utilized to study alterations in sympathetically evoked contractions of the cat nictitating membrane (CNM). MOX (1-10 microg) suppressed, dose dependently, contractions of the CNM elicited by electrically stimulating the cervical preganglionic sympathetic trunk. The suppressive effect of MOX was antagonized more effectively by EFA (333 microg) than by rauwolscine (333 microg). In contrast, RAU, but not EFA, completely reversed the suppressive effects of BRIM on electrically induced contractions of the CNM. In conclusion, these in vivo data suggest that I(1) receptors are involved in the pre-junctional (neuronal) modulation of contractions in the CNM (Supported by NIH grant EY06338).