Characteristics of CGRP-induced relaxation in rabbit ophthalmic artery.
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Animals↗
Biomedical subjects
H Uusitalo
Publications and source records attributed to H Uusitalo.
Finnish survey of public opinion about public expenditure.
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Financing, Government↗
Substance P and neurokinin A immunoreactive nerve fibres in the developing salivary glands of the rat.
The time of appearance and distribution of substance P (SP) and neurokinin A (NKA) immunoreactive nerve fibres in developing salivary glands of the rat were studied by the use of indirect immunohistochemical methods. The glands were examined at daily intervals from the 15th day in utero (i.u.) until birth, and subsequently on the 2nd, 5th, 7th, 12th, 16th and 30th postnatal day. The findings were compared to samples from adult. The first SP- and NKA-immunoreactive (IR) nerve fibres appeared on the 19th day i.u. in the parotid and submandibular glands and were abundantly distributed around developing ductal branches. In the mesenchyme around the developing ductal branches of the parotid gland the fibres appeared on the 20th day i.u. In the submandibular gland NKA-IR fibres appeared in the mesenchyme surrounding the developing ductal branches on the 19th day i.u. and SP-IR fibres on the 21st day i.u. Around blood vessels of both glands, SP- and NKA-IR fibres made their appearance only much later, on the second postnatal day. The number of SP- and NKA-IR nerve fibres in the developing salivary glands was already high on the 19th day i.u. when they were first detected. From this point up to the 16th postnatal day the glands were richly innervated by the fibres, but later the numbers slowly decreased to adult levels. The abundance of SP- and NKA-IR nerve fibres especially around the ductal branches and secretory structures in the developing salivary glands suggests a role in the functional maturation of salivary glands.
Adsorption↗
Mast cells in the anterior uvea of the rabbit. Intraocular effects of compound 48/80 in the rabbit.
In the present study, the presence and localization of mast cells and the intraocular effects of compound 48/80 have been studied in detail in the rabbit eye using histochemical and physiological methods. In histochemical studies mast cells were localized in the anterior uvea, especially in the ciliary and iridial processes. Intracamerally injected, compound 48/80 caused an increase in the intraocular pressure, disruption of the blood-aqueous barrier and an increase in the cAMP content in the aqueous humour. Miosis was observed only after higher doses of compound 48/80 (greater than 100 micrograms) and even then only one-half of the eyes responded. The intraocular effects, excluding miosis, of compound 48/80 resembled an on/off-type of response, where 20 micrograms caused only minor changes, if any, and 50 micrograms gave a maximal response. The ocular hypertensive reaction developed a tachyphylaxis so that the second and third consecutive dose of compound 48/80 (100 micrograms) produced no significant change in IOP. The results indicate that mast cells, which are present in the anterior uvea in an extent not known previously, might be involved in certain inflammatory reactions in the rabbit eye. The inconsistent and slight miosis after the intracameral application of compound 48/80 indicates that the mechanism is different from that caused by sensory nerve stimulation. The rapid development of tachyphylaxis after consecutive application of compound 48/80 suggests that mast cells are easily depleted which might be useful for further studies to evaluate the functional role of mast cells in different pathophysiological conditions in the rabbit eye.
Animals↗
Effect of topical and intracameral methysergide on calcitonin gene-related peptide-induced irritative changes in the rabbit eye.
Calcitonin gene-related peptide (CGRP) is a neuropeptide localized in the ocular sensory nerves. It is responsible for most of the irritative changes in the rabbit eye in neurogenic inflammation, namely vasodilation in the anterior uvea, breakdown of the blood-aqueous barrier and increase in the intraocular pressure. In the present study, intracameral methysergide inhibited the CGRP-induced irritative changes in the rabbit eye. Provided that sufficient concentration of methysergide could be reached in the anterior chamber after topical application, it might be possible to use locally administered methysergide to limit different pathophysiological conditions in the eye in which CGRP is involved.
Administration, Topical↗
Inhibitory effect of methysergide on calcitonin gene-related peptide-induced vasodilatation and ocular irritative changes in the rabbit.
1. Calcitonin gene-related peptide (CGRP) is involved in ocular neurogenic inflammation in the rabbit, causing vasodilatation in the anterior uvea, breakdown of the blood-aqueous barrier, increase in the intraocular pressure (IOP) and rise in the adenosine 3':5'-cyclic monophosphate (cyclic AMP) content in the aqueous humour. So far there is no means of preventing these CGRP-induced ocular effects. 2. In the present study, the effect of intravenous methysergide (1-10 mg kg-1, b.w.) on CGRP-induced changes in the IOP, blood-aqueous barrier and cyclic AMP content in the aqueous humour was studied in vivo. The effect of methysergide on CGRP-induced vasodilatation both in vivo and in vitro was also investigated. 3. Methysergide decreased intraocular pressure but had only a transient effect on blood pressure. Methysergide decreased the regional blood flow in ocular tissues by 53-65%, but did not have such a vasoconstrictor effect in most extra-ocular tissues studied. 4. Methysergide inhibited CGRP-induced vasodilatation, increase in the IOP, breakdown of the blood-aqueous barrier and increase in the cyclic AMP content in the aqueous humour in vivo. 5. In vitro, methysergide alone did not have effects on the vascular tone in isolated ophthalmic artery of rabbit. However, it potentiated noradrenaline (NA)-induced contraction. There were no differences in the IC50 values for CGRP on the NA-induced contraction in the presence and absence of methysergide, indicating that methysergide has no direct effect on the vasorelaxant effect of CGRP in vitro. 6. The present study demonstrates that in the rabbit eye methysergide inhibits CGRP-induced changes.One inhibitory mechanism of methysergide may be to enhance the effect of a vasoconstrictor (NA) to antagonize the vasodilator effect of CGRP. The present findings suggest that a methysergide-sensitive mechanism may be used to limit some pathophysiological conditions in the eye that involve neurogenic inflammation and the release of CGRP.
Animals↗
Role of endothelium and hyperpolarization in CGRP-induced vasodilation of rabbit ophthalmic artery.
The electromechanical effects of calcitonin gene-related peptide (CGRP) on intact and endothelium-denuded rabbit ophthalmic arteries were studied. CGRP inhibited norepinephrine (NE)-induced contractions. In intact arteries after washout of CGRP the contractile sensitivity to NE was increased. Conversely, in endothelium-denuded arteries, the relaxation induced by CGRP was prolonged, and after washout of CGRP the contractile sensitivity to NE was diminished. In intact arteries NE contractions were enhanced by NG-monomethyl-L-arginine (L-NMMA), an inhibitor of endothelium-derived relaxing factor (EDRF) synthesis, and in the presence of L-NMMA, CGRP-induced relaxations resembled those seen in endothelium-denuded arteries. This result suggests that there is an increased EDRF synthesis in intact arteries during NE stimulation and that CGRP may inhibit either the synthesis or the activity of EDRF. High concentrations of CGRP hyperpolarized the smooth muscle membrane both in intact and endothelium-denuded arteries. Hyperpolarizations were blocked by glibenclamide, indicating that they are mediated by activation of ATP-sensitive K+ channels. However, glibenclamide had little effect on the CGRP-induced relaxation. These results suggest that in normal physiological conditions CGRP-induced relaxation of the rabbit ophthalmic artery is mediated mainly by mechanisms other than hyperpolarization.
Adenosine Triphosphate↗
Ocular irritative response to YAG laser capsulotomy in rabbits: release of calcitonin gene-related peptide and effects of methysergide.
The Neodymium (Nd):YAG laser is commonly used in ophthalmology mainly for the posterior capsulotomy in patients with secondary cataract after extracapsular cataract extraction. A frequent side-effect following different kinds of YAG laser treatments is an acute increase in the intraocular pressure (IOP). The present study addresses the role of calcitonin gene-related peptide (CGRP) in the ocular irritative response following YAG laser anterior capsulotomy in rabbits. The YAG laser anterior capsulotomy caused an irritative response in the eye, which consisted of an increase in the IOP, miosis and breakdown of the blood-aqueous barrier. Following YAG laser capsulotomy, CGRP-immunoreactivity was found in the aqueous humour in different molecular weight forms as revealed by gel-permeation chromatography. One of the peaks coeluted with synthetic human CGRP. Methysergide attenuated the increase in the IOP and disruption of the blood-aqueous barrier, but not the miosis, following YAG laser anterior capsulotomy. The present study demonstrates the release of CGRP into the aqueous humour following YAG laser capsulotomy, and suggests that CGRP is partly causing the increase in IOP and disruption of the blood-aqueous barrier in this irritative response.
Animals↗
Anterior uveitis in children. An analysis of 75 cases with special reference to retinal anti-S antibodies.
In this prospective study of childhood uveitis, 75 children with anterior uveitis were analyzed to determine whether a relationship could be found between the occurrence of uveitis, its clinical features, and humoral immunity to retinal S-antigen. For the purposes of analysis, children were divided into acute (18 cases) and chronic (57 cases) categories, depending on the duration of ocular inflammation. Clinical features of both of these groups were compared and significant differences were found in the occurrence of unilateral vs bilateral involvement, the incidence of complications, and visual outcome. Serum samples from children with acute (7 cases) and chronic uveitis (28 cases) and from healthy children (132 cases) were tested for antibodies to S-antigen by enzyme-linked immunosorbent assay (ELISA). A statistically significant difference in the level of specific antibodies between patients with chronic uveitis and controls was found. However, there was no difference between children with acute uveitis and healthy patients, nor was there any correlation between the severity of uveitis and antibody titer. For further elucidation of the significance of circulating anti-S antibodies, 14 children with chronic anterior uveitis were followed for as long as 18 months after the initial visit. Multiple serum antibody titers to bovine retinal S-antigen were determined and compared with the clinical activity at the time of each sampling. In only 6 of 14 patients did the titers to S-antigen tend to decrease with clinical improvement and stabilize at titers somewhat higher than normal values.(ABSTRACT TRUNCATED AT 250 WORDS)
Acute Disease↗
Met5-enkephalin-Arg6-Gly7-Leu8-immunoreactive nerve fibers in the major salivary glands of the rat: evidence for both sympathetic and parasympathetic origin.
The localization of the proenkephalin A-derived octapeptide, Met5-enkephalin-Arg6-Gly7-Leu8 (MEAGL), was studied in the major salivary glands of Sprague-Dawley and Wistar rats with the indirect immunofluorescence method. MEAGL-immunoreactive nerve fibers were found around the acini, along intra- and interlobular salivary ducts and in close contact with blood vessels. In the parotid and submandibular glands tyrosine hydroxylase (TH) immunoreactivity was observed in nerve fibers around the acini, in association with intra- and interlobular salivary ducts and around blood vessels, while in the sublingual gland TH-immunoreactive nerve fibers were only seen around blood vessels. Parasympathetic neurons in submandibular ganglia contained MEAGL immunoreactivity. Moderate TH immunoreactivity was seen in some neurons of the submandibular ganglia. A subpopulation of sympathetic principal neurons in the superior cervical ganglion were immunoreactive for both MEAGL and TH. In the trigeminal ganglion, no MEAGL-immunoreactive sensory neurons or nerve fibers were observed. Superior cervical ganglionectomies resulted in a complete disappearance of TH-immunoreactive nerve fibers, while MEAGL-immunoreactive nerve fibers were still present in the glands. The presence of MEAGL immunoreactivity in neurons of both sympathetic superior cervical ganglia and parasympathetic submandibular ganglia and the results of superior cervical ganglionectomies suggest, that MEAGL-immunoreactive nerve fibers in the major salivary glands of the rat have both sympathetic and parasympathetic origin.
Animals↗
The distribution and origin of substance P immunoreactive nerve fibres in the rat conjunctiva.
Indirect immunohistochemistry was used to examine the presence and origin of substance P immunoreactive nerve fibres in the rat conjunctiva. Fluorescent substance P immunoreactive nerve fibres were visualized both in the epithelium and stroma, their number being higher in the stroma where they were associated with blood vessels, the smooth muscle of Müller and the Meibomian glands. Ten to twenty percent of the ganglion cells in the trigeminal ganglion were immunoreactive to substance P, most of them being small in size. Sensory denervation by electrocoagulating the ophthalmic and maxillary branches of the trigeminal nerve caused a complete disappearance of the epithelial fibres and greatly reduced the number of the stromal fibres. These results indicate that the majority of the demonstrated fibres are sensory nerves originating from the trigeminal ganglion. Since sympathectomy had no detectable effect on the number or distribution of substance P immunoreactive nerve fibres, and since some of the fibres remained after sensory denervation it is suggested that at least some of the remaining fibres could be of parasympathetic origin.
Animals↗
Neurokinin A in the parotid and submandibular glands of the rat: immunohistochemical localization and effect on protein and peroxidase secretion.
An indirect immunofluorescence technique was used to study the distribution of neurokinin A immunoreactive (NKA-IR) nerve fibres in submandibular and parotid glands of the rat. The functional role of neurokinin A on protein and peroxidase secretion in these glands was evaluated by using in vitro methods. In the parotid gland neurokinin A immunoreactive fibres were mainly distributed around the secretory acini, but some were also in evidence around the stromal blood vessels and ducts. The number of the neurokinin A immunoreactive nerve fibres was lower in the submandibular gland than in the parotid gland. They were mainly distributed around the secretory acini and stromal blood vessels and ducts. In vitro, neurokinin A significantly stimulated the release of total amount of released proteins and peroxidase from parotid gland fragments, while in the submandibular gland only the release of peroxidase was increased. By using SDS polyacrylamide gel electrophoresis (SDS-PAGE) specific changes were found in the release of proteins after neurokinin A stimulation. The results of the present study demonstrate that neurokinin A immunoreactive nerve fibres are present in the rat parotid and submandibular glands. Their localization around the secretory elements of the glands and the effect of neurokinin A in vitro experiments indicates that neurokinin A might have a significant role in the regulation of salivary secretion.
Animals↗
Serotonergic responses in rabbit ophthalmic artery: a pharmacological characterization.
The contractile effect of serotonin (5-HT) on rabbit ophthalmic artery was studied. In a solution containing 20 mM K+ 5-HT induced a biphasic dose-response curve (DRC) in intact arteries. At normal extracellular K+ concentration ([K+]o), only high concentrations of 5-HT (greater than or equal to 1 microM) were able to induce contraction. In endothelium-denuded arteries 5-HT induced a DRC at normal [K+]o, which resembled that in intact arteries at 20 mM [K+]o. The high-potency portion of the 5-HT DRC was inhibited only by metitepine, whereas the low-potency portion was blocked by metitepine, methysergide, spiperone, and ketanserin, indicating that in this preparation the 5-HT1 receptor subtypes are more sensitive to 5-HT than the 5-HT2 receptor subtypes. Cyanopindolol had no effect on 5-HT-induced contraction. 8-Hydroxy-2-(di-n-propylamino)tetralin gave a contraction at high concentrations (greater than or equal to 0.1 microM), which was not blocked by cyanopindolol. The contractile response to 5-methoxytryptamine was similar to that for 5-HT. The results indicate that the 5-HT1 receptors of the ophthalmic artery belong either to 1C or 1D subtypes. 2-Methylserotonin, an agonist for 5-HT3 receptor, had no contractile effect on rabbit ophthalmic artery. The effect of prior exposure to 5-HT on norepinephrine (NE)-induced contraction was also studied. In intact arteries prior exposure to a low 5-HT concentration (10 nM) induced attenuation and prior exposure to a high 5-HT concentration (1 microM) gave potentiation of the NE-induced contraction.(ABSTRACT TRUNCATED AT 250 WORDS)
5-Methoxytryptamine↗
Intraocular and cardiovascular effects of calcitonin gene-related peptide (CGRP)-I and -II in the rabbit.
Calcitonin gene-related peptide (CGRP) is a 37-amino acid neuropeptide localized in the eye in the sensory nerves. In this study, the physiological effects of the two naturally occurring forms of human CGRP, CGRP-I, and -II, which differ only in three amino acids, have been demonstrated in the rabbit eye and cardiovascular system. Intravenously administered CGRP-I caused a biphasic increase in the intraocular pressure (IOP), disruption of the blood-aqueous barrier, and increase in the cyclic adenosine 3',5'-monophosphate (cAMP) content in the aqueous humor. CGRP-II caused a monophasic increase in the IOP and disruption of the blood-aqueous barrier, but no increase in the cAMP content occurred. CGRP-I and -II decreased the blood pressure in a similar dose-dependent manner. The effects of intracamerally administered CGRP-I and -II were very similar in the eye. An increase in the IOP, breakdown of the blood-aqueous barrier, and an increase in the cAMP content in the aqueous humor occurred. The differences in the biological responses between CGRP-I and -II in the rabbit eye might be a result of the different affinities of the CGRP forms to a single receptor. Alternatively, different subtypes of receptors for CGRP-I and -II may exist in the rabbit.
Animals↗
Calcitonin gene-related peptide immunoreactive nerve fibers in the rat conjunctiva.
Calcitonin gene-related peptide (CGRP) immunoreactive nerve fibers were studied in the rat conjunctiva by using indirect immunohistochemistry. Their origin was evaluated in a series of experiments where the animals were denervated by electrocoagulating the two first branches of the trigeminal nerve or by surgically extirpating the superior cervical ganglion. The CGRP-immunoreactive nerve fibers were seen mainly as thin varicose fibers in the epithelium and in the stroma. Many of the stromal fibers showed no apparent destination. However, CGRP-immunoreactive fibers were commonly found in association with stromal blood vessels, the smooth muscle of Müller, and the meibomian glands. Approximately 40% of the ganglion cells in the trigeminal ganglion were immunoreactive to CGRP. In the superior cervical ganglion, a few CGRP-immunoreactive fibers were seen although the ganglion cells were negative. After trigeminal denervation, all the epithelial and most of the stromal CGRP-immunoreactive nerve fibers disappeared. Sympathectomy had no effect on the presence of the CGRP-immunoreactive fibers. These observations indicate that most of the CGRP-immunoreactive nerve fibers in the rat conjunctiva are sensory nerves originating in the trigeminal ganglion. A few of the demonstrated fibers are, however, resistant to the sensory denervation and may be parasympathetic in their origin.
Animals↗
CGRP-immunoreactive sensory nerve fibers in the submandibular gland of the rat.
Indirect immunofluorescence technique was used to study the occurrence and distribution of CGRP immunoreactivity in the submandibular gland of normal rats and after unilateral sensory and sympathetic denervations. In normal rats, CGRP-immunoreactive nerve fibers and nerve trunks were seen around or in close contact with interlobular salivary ducts as well as around small blood vessels of the gland. Occasionally, CGRP-immunoreactive nerve fibers were also detected between or around the acini of the gland. The submandibular ganglia contained CGRP-immunoreactive nerve fibers, but the ganglion cells were not immunoreactive for CGRP. The trigeminal ganglion contained a population of CGRP-immunoreactive, mainly small sized ganglion cells and nerve fibers distributed throughout the ganglion. Unilateral electrocoagulation of the trigeminal nerve caused a significant reduction in the number of immunoreactive nerve fibers in the gland, although some fibers still were present in the ipsilateral glandular tissue. Unilateral superior cervical ganglionectomy caused no detectable effect on the number of CGRP-immunoreactive nerve fibers in the gland. The present results suggest that the rat submandibular gland contains CGRP-immunoreactive nerve fibers both around blood vessels and in glandular secretory elements. Denervation experiments support the view that the majority, but perhaps not all of them originate from the trigeminal ganglion.
Animals↗
Nerve fibers showing immunoreactivities for proenkephalin A-derived peptides in the lacrimal glands of the guinea pig.
The extra- and intraorbital lacrimal glands of guinea pigs were studied for the presence and distribution of enkephalin-like immunoreactive nerve fibers. Four specific antisera against the four different enkephalin sequences contained in pre-proenkephalin A (Met-Enk, Met-Enk-Arg-Phe, Met-Enk-Arg-Gly-Leu, and Leu-Enk) were used. All of these immunoreactivities were identically distributed in varicose nerve fibers in both the extra- and intraorbital lacrimal glands. These fibers densely surrounded the glandular acini and also innervated the secretory ducts. Sympathetic denervation had no effect on these nerve fibers. The results suggest that enkephalins derived from proenkephalin A may play a role in the nervous control of the lacrimal secretion.
Animals↗
Platelets and polymorphonuclear leukocytes in experimental ocular inflammation in the rabbit eye.
Accumulation of 111indium-oxine (111In)-labelled platelets and the kinetics of 111In-labelled polymorphonuclear leukocytes (PMNLs) were studied in the anterior eye during neurogenic inflammation (induced by topical neutral formaldehyde) or after paracentesis in the rabbit, after formaldehyde irritation, 40 times more platelets were found in the aqueous humor 60 min later than in the control eyes and 400 times more after paracentesis. Platelets were found to be increased in the ciliary body, but not in the iris or choroid. Under light microscopy, some of the blood vessels in the ciliary processes were occluded and filled with red blood cells and platelets. The amount of PMNLs increased in the aqueous humor 15-20 h following formaldehyde irritation. After paracentesis, increased amounts of PMNLs were found in the iris and ciliary body 3-6 h later, while in the aqueous humor PMNLs were observed already 2 h. In the present study, increased amounts of 111In-labelled platelets and PMNLs were demonstrated in the anterior eye during experimental ocular inflammation. This method provides a useful tool for evaluating the accumulation of cells or the cell kinetics in ocular tissues during experimental inflammation.
Animals↗