Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ability of 1-[6-[[17 beta-3-methoxyestra-1,3,5(10)-trien-17- yl]amino]hexyl]-1H-pyrrole-2,5-dione (U73122), an inhibitor of phospholipase C (Smith et al., J Pharmacol Exp Ther 253:688-697, 1992), to inhibit agonist-stimulated and store-operated Ca2+ inflow in single hepatocytes was investigated with the aim of testing whether the activation of phospholipase C is a necessary step in the process of agonist-stimulated Ca2+ inflow in this cell type. U73122 inhibited the release of Ca2+ from intracellular stores and plasma membrane Ca2+ inflow induced by vasopressin. An inactive analogue of U73122, 1-[6-[[17 beta-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]- 2,5-pyrrolidone-dione (U73433), did not inhibit vasopressin-induced release of Ca2+ from intracellular stores, but did partially inhibit Ca2+ inflow. Neither U73122 nor 'inactive' analogue U73433 inhibited the release of Ca2+ from intracellular stores when this was initiated by the photolysis of 'caged' guanosine (5'-[gamma-thio]triphosphate (GTP gamma S) introduced to the cytoplasmic space by microinjection. However, both compounds inhibited GTP gamma S-stimulated Ca2+ inflow. U73122 also inhibited the actions of glycerophosphoryl-myo-inositol-4,5-diphosphate (GPIP2), a slowly-hydrolysed analogue of inositol 1,4,5-triphosphate (InsP3) which is released by photolysis of 'caged' 1-(alpha-glycerophosphoryl)-myo-inositol-4,5-diphosphate, P4(5)-1-(2-nitrophenyl)ethyl ester, and thapsigargin in stimulating Ca2+ inflow. U73122 did not inhibit GPIP2-stimulated release of Ca2+ from intracellular stores, but did partially inhibit the ability of thapsigargin to induce Ca2+ release. It is concluded that, while U73122 does inhibit phospholipase C beta in hepatocytes, complete inhibition of this enzyme in situ requires an intracellular concentration of U73122 higher than that achieved in the present experiments. Moreover, both U73122 and 'inactive' analogue U73433 have one or possibly two additional sites of action. These are likely to be the hepatocyte plasma membrane Ca2+ inflow channel protein (or a protein involved in the activation of this channel by the InsP3-sensitive intracellular Ca2+ store), and a protein involved in thapsigargin action.
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PMID:Evidence obtained using single hepatocytes for inhibition by the phospholipase C inhibitor U73122 of store-operated Ca2+ inflow. 776 79

It is often believed that increases in intracellular Ca2+ ([Ca2+]i) resulting from stimulation of G-protein coupled receptors in vascular smooth muscle cells (VSMC) require activation of the beta1 isoform of phospholipase C (PLC). However, recent studies showed that rat aortic VSMC do not express PLC beta-1 and that stimulation with angiotensin-II induces tyrosine kinase dependent increases in [Ca2+]i and tyrosine phosphorylation of PLC gamma-1. Whether this pathway is activated by other vasoactive agents that stimulate G-protein coupled receptors is unknown. Here, we show that A10 VSMC express PLC beta-2, PLC beta-3, PLC delta-1, and PLC gamma-1. The cells also expressed Galpha(q/11). However, neither PLC beta-1 nor PLC beta-4 was detected. Stimulation with angiotensin-II, vasopressin, serotonin, or endothelin induced tyrosine kinase dependent increases in [Ca2+]i. However, tyrosine phosphorylation of PLC gamma-1 did not occur. In contrast, stimulation with platelet derived growth factor increased [Ca2+]i and tyrosine phosphorylation of PLC gamma-1. The results show that tyrosine phosphorylation of PLC gamma-1 is not required for tyrosine kinase dependent increases in [Ca2+]i resulting from stimulation of diverse G-protein coupled receptors in VSMC.
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PMID:Stimulation of G-protein coupled receptors in vascular smooth muscle cells induces tyrosine kinase dependent increases in calcium without tyrosine phosphorylation of phospholipase C gamma-1. 947 75

The prevalence of nocturia in patients with multiple sclerosis (MS) is high, ranging from 20.9% to 48.8% in this population. Its underlying pathophysiology is complex and different from the non-neurogenic population. In the MS population, the pathophysiology may involve neurogenic lower urinary tract dysfunction (NLUTD) such as detrusor overactivity (NDO), detrusor-sphincter dyssynergia, or detrusor underactivity resulting in reduced bladder capacity. Nocturnal polyuria is also a significant contributor to the pathogenesis of nocturia in MS patients and may be the result of specific mechanisms such as nocturnal hypertension through autonomic cardiovascular dysfunction or lack of diurnal variation of antidiuretic hormone production (ADH) due to demyelinating lesions of the spinal cord. Nocturia might be particularly burdensome in MS patients by contributing to fatigue, a common and highly debilitating symptom in this population. There is likely a complex and multidirectional relationship between nocturia, other sleep disorders, and fatigue in the MS population that has yet to be explored. The assessment of nocturia in MS should rely upon a thorough history and physical examination. Urinalysis should be done to rule out urinary tract infection, a frequency-volume chart might help elucidating the underlying mechanisms, and post-void residual volume may be of interest to screen for urinary retention that could be asymptomatic in MS patients. Other tests such as urodynamics or polysomnography are indicated in selected patients. The treatment should be tailored to the underlying cause. The first steps involve behavioral interventions and treatment of cofactors. When possible, the predominant mechanism should be addressed first. In case of predominant NDO, antimuscarinics and beta-3 agonists should be offered as a first-line treatment and intradetrusor injections of botulinum toxin as a second-line treatment. In cases of incomplete bladder emptying, clean-intermittent self-catheterization is often used as part of multiple other interventions. In cases of nocturnal polyuria, desmopressin may be offered, inclusive of use of newer formulations (desmopressin acetate nasal spray, desmopressin orally disintegrated tablet) in countries where they are approved.
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PMID:Nocturia in Patients With Multiple Sclerosis. 3176 33