Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.1 (adenylate cyclase)
 19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Eight weeks following streptozotocin-induced diabetes mellitus in rats, the sensitivity of adenylate cyclase to dopamine (DA) and norepinephrine (NE) was reduced in homogenates of retina. Furthermore, the activation of adenylate cyclase in cerebral microvessels (capillaries) by NE, 5'-guanylyl imidodiphosphate (alone or with NE) and forskolin was reduced in diabetic rats versus appropriate controls. In diabetic rats enzyme sensitivity to only NE was attenuated in homogenates of cerebral cortex and cortical piaarachnoid. No differences between controls and diabetics were noted with respect to guanylate cyclase or cyclic AMP phosphodiesterases. The damage observed in retina and microvessels may play an important pathogenic role in diabetes-induced blindness and stroke.
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PMID:Streptozotocin-induced diabetes produces alterations in adenylate cyclase in rat cerebrum, cerebral microvessels and retina. 613 68

Immune privilege is a physiologic mechanism within the eye which protects it against pathogens, while also protecting it from inflammation. Immunological mechanisms in the eye must be tightly regulated to ensure externally mediated injury and infection or internally mediated autoimmunity do not exceed self-defence tolerance. Vasoactive neuropeptides (VNs) including vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase polypeptide (PACAP) and their receptors exist in the mammalian eye including the sclera, cornea, iris, ciliary body, ciliary process and the retina and may have a role in protecting these normally immune privileged sites. VN receptors are class II G protein-coupled receptors (GPCRs) which couple primarily to the adenylate cyclase (AC)-cyclic AMP pathway. A sound blood supply is essential for retinal survival hence vascular compromise will have serious consequences. Retinal vasculitis is a potentially blinding condition with a strong association with systemic inflammatory diseases. Compromise of the endothelial barriers and the blood retina barrier (BRB) may instigate inflammatory responses setting up a chain of events involving VNs in a manner which provokes autoimmunity to them. Protection from BRB breakdown may be linked to nitric oxide (NO) effects and actions of phosphodiesterase inhibitors and cAMP production. Induced NO expressed under influences of inflammatory mediators evokes neurodegeneration and cell apoptosis and may lead to serious ocular disease including retinal injury. Other inflammatory mediators also play a role in retinal pathology. PACAP and glutamate are co-stored in the retinohypothalamic tract and PACAP attenuates glutamate induced neurotoxicity in cultured retinal neurons suggesting that compromise of this VN would have significant detrimental impact on retinal viability though glutamate toxicity. Additional effects of VN compromise would possibly occur through unopposed vasoconstriction and inflammation. Proof of this hypothesis has important implications for treatment and prevention of autoimmune retinopathy and blindness as a number of therapeutic pathways may be opened. Importantly for therapeutic contexts cAMP effects are maintained by phosphodiesterase (PDE) inhibitors which could be used in VN autoimmune disorders. A compelling case may exist to undertake a therapeutic trial of VN replacement, PDE inhibitors and other agents in autoimmune retinopathies resulting from possible VN autoimmunity.
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PMID:Does autoimmunity of endogenous vasoactive neuropeptides cause retinopathy in humans? 1756 49

The multiplicity of peptidergic receptors and of the transduction pathways they activate offers the possibility of important advances in the development of specific drugs for clinical treatment of central nervous system disorders. Among them, retinal ischemia is a common clinical entity and, due to relatively ineffective treatment, remains a common cause of visual impairment and blindness. Ischemia is a primary cause of neuronal death, and it can be considered as a sort of final common pathway in retinal diseases leading to irreversible morphological damage and vision loss. Neuropeptides and their receptors are widely expressed in mammalian retinas, where they exert multifaceted functions both during development and in the mature animal. In particular, in recent years somatostatin and pituitary adenylate cyclase activating peptide have been reported to be highly protective against retinal cell death caused by ischemia, while data on opioid peptides, angiotensin II, and other peptides have also been published. This review provides a rationale for harnessing the peptidergic receptors as a potential target against retinal neuronal damages which occur during ischemic retinopathies.
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PMID:The Neuropeptide Systems and their Potential Role in the Treatment of Mammalian Retinal Ischemia: A Developing Story. 2381 41