The purpose of this study was to investigate mechanisms of suppression of norepinephrine release by 7-OH-DPAT, a dopamine D₂/D₃ receptor agonist, in PC12 cells pretreated with nerve growth factor (NGF). 7-OH-DPAT caused inhibition of basal and K⁺-evoked norepinephrine release, which could be blocked by pretreatment with raclopride, a D₂/D₃ receptor antagonist. Moreover, dopamine D₂ and D₃ receptors were identified by immunocytochemistry. Expression of D₂, D₃, and D₄ mRNAs and their proteins were detected using RT-PCR and immunoblotting. Furthermore, 7-OH-DPAT produced no change in cGMP levels; however, 7-OH-DPAT inhibited forskolin-stimulated cAMP accumulation that was antagonized by pretreatment with raclopride. In addition, 7-OH-DPAT inhibited carbachol-induced Ca²⁺ transient, conversely, 7-OH-DPAT had no effect on 4-aminopyridine-induced Ca²⁺ transient. Taken together, suppression of cAMP accumulation and calcium mobilization by 7-OH-DPAT is involved in the inhibition of norepinephrine release through activation of dopamine D₂/D₃ receptors.

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Summary Background Type I mammalian collagens have several photolabile fluorescent moieties that absorb UV rays capable of reaching the dermis. We studied the temperature dependence of fluorescence fading as a marker of photochemical damage. Methods Collagen solutions were exposed to radiation from 0 to 240 min from either a UVG-11 hand lamp, total dose = 1.173 × 103 J/m2; a UVL-21 hand lamp total dose = 2.030 × 103 J/m2; or the fluorometer, at 325 ± 5 nm, total dose = 0.156 × 103 J/m2. We recorded intensities at excitation/emission wavelengths 270/300, 270/330, 270/360, 270/400, 325/400, and 370/450 nm at T = 9.0–59.3 1°C. Results Results indicated simultaneous forward and reverse reactions. However, the 270/360 nm fluorophore could be analyzed as a second-order reaction. The Arrhenius curve showed two straight lines intersecting near the denaturation temperature, with helix activation energy Ea~0 and coil Ea = 7.6 ± 0.6 kcal/mol (31.7 ± 2.5 kJ/mol). Discussion Collagen-bound fluorophores are not just passive markers of oxidative stress and age-related damage. Their photolability to wavelengths reaching the dermis may result in pathological conditions, particularly at elevated body temperatures.

The purpose of this study was to determine the potential role of brain natriuretic peptide (BNP) in the PD128,907 (a dopamine D2/D3 receptor agonist)-induced ocular hypotension in rabbits. The effects of topical application of PD128,907 (75, 250, 750 microg) on intraocular pressure (IOP) were investigated. The lowest dose (75 microg) did not alter IOP; while the higher doses (250 and 750 microg) reduced IOP bilaterally. The PD128,907 (250 microg)-induced ocular hypotension, which lasted 3 hours, could be blocked by raclopride (1000 microg), a dopamine D2/D3 receptor antagonist, as well as by sympathetic denervation. Aqueous humor inflow was reduced by intravitreal injection of PD128,907 (10 microg) by 67% at 1 and 2 hours, which then returned to baseline at 3 hours. Furthermore, topical application of PD128,907 (250 microg) elevated aqueous BNP levels by 3-fold at 30 minutes, 6-fold at 1 hour and 5-fold at 2 hours, which could be blocked by pretreatment with raclopride (250 microg). Taken together, PD128,907-induced ocular hypotension by activation of dopamine D2/D3 receptors. This action was associated with reduced aqueous humor inflow and increased aqueous BNP levels.

The purpose of this study is to determine the mechanisms of action involved in the ocular hypertension induced by 4-aminopyridine (4-AP), a voltage-dependent potassium (K⁺) channel blocker, in rabbits. Topical application of 4-AP elevated intraocular pressure (IOP). This action caused increases in the aqueous flow rate as well as aqueous levels of protein and norepinephrine. In isolated iris-ciliary body preparations, 4-AP (0.01, 0.1, 1 mmol/l) caused dose-related increases in field-stimulated norepinephrine release by 43, 222 and 243%, respectively. Taken together, the IOP-elevating effect evoked by 4-AP was associated with enhancement of aqueous norepinephrine levels and norepinephrine release from sympathetic nerves of the iris-ciliary body. These results demonstrate that the 4-AP-sensitive K⁺ channels in sympathetic nerves and the ciliary epithelium are the potential sites of action of the 4-AP-induced ocular hypertension.