Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide of the vasoactive intestinal peptide/secretin/glucagon superfamily. Studies in two related patients with a partial trisomy 18p revealed three copies of the PACAP gene and elevated PACAP concentrations in plasma. The patients suffer from severe mental retardation and have a bleeding tendency with mild thrombocytopenia, and their fibroblasts show increased PACAP mRNA levels. The PACAP receptor (vasoactive intestinal peptide/pituitary adenylate cyclase-activating peptide receptor 1 [VPAC1]) in platelets and fibroblasts is coupled to adenylyl cyclase activation. Accordingly, we found increased basal cAMP levels in patients' platelets and fibroblasts, providing a basis for the reduced platelet aggregation in these patients. Megakaryocyte-specific transgenic overexpression of PACAP in mice correspondingly increased PACAP release from platelets, reduced platelet activation, and prolonged the tail bleeding time. In contrast, the PACAP antagonist PACAP(6-38) or a monoclonal PACAP antibody enhanced the collagen-induced aggregation of normal human platelets, and in PACAP knockout mice, an increased platelet sensitivity toward collagen was found. Thus, we found that PACAP modulates platelet function and demonstrated what we believe to be the first hemostatic defect associated with PACAP overexpression; our study suggests the therapeutic potential to manage arterial thrombosis or bleeding by administration of PACAP mimetics or inhibitors, respectively.
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PMID:The pituitary adenylate cyclase-activating polypeptide is a physiological inhibitor of platelet activation. 1506 23

We describe a Japanese brother and sister with Martsolf syndrome. They had short stature, severe mental retardation, cataract, hypogonadism, craniofacial dysmorphism, and bone and joint symptoms including scoliosis, lax finger joints, and talipes valgus. Previously undescribed findings included proximal femoral epiphyseal dysplasia reminiscent of Legg-Calve-Perthes disease in both patients, and Klippel-Feil malformation and osteopathia striata in one patient. Brain MRI showed mild frontal and temporal lobe atrophy, and mild ventricular enlargement. Severe GH deficiency was demonstrated after insulin tolerance and glucagon/propranolol tolerance tests. No responses to serum LH and FSH after a gonadotropin-releasing hormone (GnRH) test suggested secondary hypogonadism, that is, hypogonadotropic hypogonadism, due to hypothalamus-pituitary axis insufficiency in both patients.
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PMID:Martsolf syndrome in Japanese siblings. 1739 1