Search

The regulation of neostriatal cholinergic function by tachykinins (TKs) has been studied by measuring endogenous ACh released from rat neostriatal slices. Septide (SEP; a highly selective substance P analog), neurokinin A (NKA), and neurokinin B (NKB) elicited endogenous ACh release in a concentration-dependent manner. The rank order in potency was the following: NKB (EC50 approximately 0.5 nM) greater than NKA (EC50 approximately 7 nM) greater than SEP (EC50 approximately 12 nM). Spantide (SPA) was less effective (39% inhibition) than [D-Arg6, D-Trp7,9, N-Methyl-Phe8]-substance P fragment 6-11 (53% inhibition) at antagonizing ACh release evoked by SEP and NKA. Smaller doses of the antagonists inhibited the effects of SEP compared to NKA, and the effects of NKB could only be antagonized by SPA. These findings suggest the involvement of the three neurokinin (NK) receptors in ACh release evoked by TKs with the following rank order: NK3 greater than NK2 greater than NK1. 6-Hydroxydopamine lesions of nigrostriatal neurons and tetrodotoxin (TTX) intoxication of striatal tissue revealed two different patterns of regulation of cholinergic function by TKs. On the one hand, SEP and NKA evoked ACh release, independently of the nigrostriatal dopaminergic system, by acting on NK1 and NK2 receptors that are probably localized on the somatodendritic field of cholinergic neurons receiving substance P terminals. On the other hand, dopaminergic terminals seem to regulate NKB neurons that modulate cholinergic neurons, because NKB-evoked ACh release decreased by 24% in the denervated striata. In addition, TTX partially blocked (50%) ACh release evoked by NKB, suggesting that NKB acts on NK3 receptors at both the nerve terminals and the somatodendritic field of cholinergic neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

We describe a technique and report a retrospective evaluation of myopic keratomileusis in situ. Surgery was performed on 32 eyes, with a mean follow-up time of 128.7 days (range 90 to 194 days). The average reduction of myopia was 8.48 diopters (D) when measured by refraction and 3.96 D by keratometry (minor axis). A statistically significant Pearson correlation coefficient of 0.49 (P = .01) was found between these two variables. Postoperative mean manifest spherical equivalent was -1.70 D (standard deviation 2.54 D). Mean cylinder correction increased -0.48 D (range -2.25 to 2.00 D). Uncorrected visual acuity improved after surgery in all eyes, but in 14 eyes the best corrected visual acuity diminished. Multiple regression model disclosed a limited predictability of the technique. Complications included diminution of best corrected visual acuity, under- and overcorrections, increase in keratometric astigmatism and cylinder correction, keratitis, delayed corneal epithelialization, interface amorphous deposits, monocular diplopia, interface epithelialization, and opacification. The most frustrating was an elusive postoperative cycloplegic refraction. In our hands, myopic keratomileusis in situ was not a technically safe, precise, and predictable technique for correction of myopia. Further improvement in the technique and equipment may provide better results.

In order to study the role of the dopaminergic system in the mu- or delta-opioid inhibition of endogenous acetylcholine release evoked by glutamate, we blocked the dopaminergic transmission with dopaminergic antagonists and/or 6-hydroxydopamine lesions. In all these experimental conditions we show that dopaminergic antagonists by themselves could not modify the glutamate-evoked acetylcholine release, and the selective D1 antagonist (SCH 23390) was unable to modify the mu- or delta-opioid inhibition of glutamate-evoked acetylcholine release. However, in the non-lesioned animals and in the contralateral striata to 6-hydroxydopamine lesions, D2 antagonists (haloperidol or sulpiride, 10 microM) prevented the effects of delta-opiate agonists ([D-Ala2, D-Leu5]enkephalin, 1 microM and [D-Pen2, D-Pen5]enkephalin, 0.1 microM), but not the effects of mu-opiate agonists (morphine or [D-Ala2, Gly(ol)5]enkephalin, 1 microM). Furthermore, [D-Ala2, D-Leu5]enkephalin inhibition of glutamate-evoked acetylcholine release was prevented by D2 antagonists in a concentration-dependent manner. Instead, in the 6-hydroxydopamine-lesioned side, while [D-Ala2, D-Leu5]enkephalin (1 microM) inhibition of glutamate-evoked acetylcholine release was completely abolished, morphine (1 microM) inhibition remained unchanged. We conclude that the inhibition of glutamate-evoked endogenous acetylcholine release by delta-opiate agonists, unlike mu-opiate agonists, depends on dopaminergic terminals and D2 receptors. Furthermore, these results suggest that the inhibition by delta-opiate agonists could be the result of dopamine release from dopaminergic terminals and its action on D2 receptors.

We have examined the role of the GABAergic system in the opioid inhibition of endogenous acetylcholine (ACh) release from rat neostriatal slices by blocking either gamma-aminobutyric acid-A (GABAA) or GABAB receptors. GABAergic antagonists (bicuculline or phaclofen) completely blocked mu- (morphine or DAGO) and delta-opioid (DPDPE) inhibition of glutamate-evoked endogenous ACh release in a concentration-dependent manner. However, GABA antagonists were ineffective in blocking the opioid inhibition of potassium-evoked endogenous ACh release. These findings point to the important role of the GABAergic system in the regulation of mu- and delta-opioid inhibition of cholinergic neurons stimulated by glutamate.

Endogenous acetylcholine (ACh) release from rat striatal slices was measured by a chemiluminescent method. Several opiate agents were tested for their ability to modulate ACh release evoked by potassium ions (K+) or glutamic acid (GLU). Morphine, [D-Ala2,Gly(0l)5]-enkephalin (DAGO), [D-Ala2,D-Leu5]-enkephalin (DADLE) and [D-Pen2-D-Pen5]-enkephalin (DPDPE) were found to have an inhibitory effect on K(+)- or GLU-evoked ACh release. This effect was completely blocked by naloxone, but this antagonist by itself had no effect on ACh release. The action of mu-opiate agonists (morphine and DAGO) on ACh release evoked by K+ was sensitive to tetrodotoxin (TTX), but that of delta-opiate agonists (DADLE and DPDPE) was insensitive. The release evoked by GLU was abolished in the presence of TTX. The activation of kappa-opiate receptor by dynorphin-(1-13) had no effect on K(+)- or GLU-evoked ACh release. It is concluded that mu- and delta-opiate agonists, but not kappa, exert an inhibitory control on striatal cholinergic interneurons, but with a different mechanism of action of localization of the receptors. Corticostriatal glutamatergic neurons have an important role in the interaction of the ACh-opioid systems.

Endogenous acetylcholine release from rat striatal slices in response to several excitatory amino acids and its regulation by gamma-aminobutyric acid were investigated using a chemiluminescent reaction to detect this release continuously. The amount of acetylcholine released by glutamate (1 ?M) was 60% of that released by KCl (50 mM). Quisqualic acid and kainic acid, both 1 ?M, elicited only half as much acetylcholine release as did 1 ?M of glutamic acid or N- methyl- d -aspartate . Only the effects of glutamate or N- methyl- d -aspartate were blocked by ?-aminoadipic acid, but not by glutamic acid diethylester, both at 100 ?M. Gamma-aminobutyric acid modulated acetylcholine release evoked by either high potassium or glutamate. However, the inhibitory effect of gamma-aminobutyric acid was greater (54%) when the slices were stimulated by glutamate than when depolarized by KCl (40%). These actions were completely reversed by picrotoxin or bicuculline, both at 100 ?M. It is concluded on the one hand that glutamate elicits acetylcholine release by acting on the N- methyl- d -aspartate receptor. On the other hand, gamma-aminobutyric acid inhibited to a greater extent endogenous acetylcholine release evoked by glutamate than that evoked by potassium. These findings suggest that gamma-aminobutyric acid exerts an important regulation on cholinergic neurons stimulated by the glutamatergic corticostriatal pathway.

The precorneal tear film is important in preserving the integrity of the corneal epithelium. One of several quantitative and qualitative clinical evaluation of the tear film is the determination of break-up time (BUT). Although controversial, this test is an important index of tear film physiology. The test depends upon the viscosity, surface tension and geometry of the tear film. The system is therefore ill-defined and current practices of bio-microscopic examination do not take into account the real nature of the called "dry spot". In this paper, we describe an innovative method of microscopic examination of the wetting film formed on the eye. The method is based on physico-chemical studies of thin wetting film (thin liquid film formed on solid surface). A freshly enucleated eye is immerged in a physiological solution and a thin wetting film is formed by bringing an air bubble into contact with a corneal epithelium. The examination of the wetting film is done using a specially-constructed device which simultaneously enables the deliver of an air bubble and the ability to observe the formed bubble. The observed interference colours provide information about the thickness and homogeneity of the liquid film. One can also observe the nature of lipid droplets floating at the surface of the tear aqueous phase by this technique. The study of the stability and rupture of thin films formed on freshly enucleated normal rabbit or rat eyes shows that the corneal epithelium is perfectly wettable as long as the epithelial cells had not suffered any irreversible damage. "Dry spot" are in reality microscopically thin fluid films with a thickness of several hundred nanometers.