Calcitonin gene-related peptide inhibits human platelet aggregation. 1996

Y Matsumoto, and S Ueda, and S Matsushita, and T Ozawa, and H Yamaguchi
Department of Internal Medicine, Juntendo University, School of Medicine, Tokyo, Japan.

Calcitonin gene-related peptide (CGRP) is a potent vasodilator in humans. CGRP receptors have also been found in various tissues other than blood vessels, such as the central nervous system, kidney, and heart. However, little is known about the effects of CGRP on human platelets. We investigated the effect of CGRP (human alpha type) on platelet aggregation in 21 healthy subjects (9 men and 12 women, mean age 54.6 years). CGRP inhibited platelet aggregation in vitro in 19 of the subjects (90.5%) in a dose-dependent manner with 50% inhibitory doses of 1.6 mumol/L and 1.1 mumol/L for aggregation induced by epinephrine and collagen, respectively. 125I-labeled CGRP bound specifically to intact platelets. The dissociation constant (Kd) was 61.9 +/- 17.7 pmol and the maximum number of binding sites (Bmax) was 5.4 +/- 3.9 pmol/10(9) platelets. The CGRP analogue (8-37)CGRP, but not calcitonin, inhibited the binding of 125I-CGRP to platelets. CGRP (5 mumol/L), but not (8-37)CGRP or calcitonin, increased the platelet cyclic AMP (cAMP) concentration by 31.7 +/- 3.6%. Thus, CGRP inhibits platelet aggregation via a specific receptor and by increasing the platelet cAMP concentration. CGRP may play a role in the modulation of platelet function in humans.

UI MeSH Term Description Entries
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D010446 Peptide Fragments Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques. Peptide Fragment,Fragment, Peptide,Fragments, Peptide
D010974 Platelet Aggregation The attachment of PLATELETS to one another. This clumping together can be induced by a number of agents (e.g., THROMBIN; COLLAGEN) and is part of the mechanism leading to the formation of a THROMBUS. Aggregation, Platelet
D010975 Platelet Aggregation Inhibitors Drugs or agents which antagonize or impair any mechanism leading to blood platelet aggregation, whether during the phases of activation and shape change or following the dense-granule release reaction and stimulation of the prostaglandin-thromboxane system. Antiaggregants, Platelet,Antiplatelet Agent,Antiplatelet Agents,Antiplatelet Drug,Blood Platelet Aggregation Inhibitor,Blood Platelet Antagonist,Blood Platelet Antiaggregant,PAR-1 Antagonists,Platelet Aggregation Inhibitor,Platelet Antagonist,Platelet Antagonists,Platelet Antiaggregant,Platelet Antiaggregants,Platelet Inhibitor,Protease-Activated Receptor-1 Antagonists,Antiplatelet Drugs,Blood Platelet Aggregation Inhibitors,Blood Platelet Antagonists,Blood Platelet Antiaggregants,Platelet Inhibitors,Agent, Antiplatelet,Aggregation Inhibitor, Platelet,Antagonist, Blood Platelet,Antagonist, Platelet,Antiaggregant, Blood Platelet,Antiaggregant, Platelet,Drug, Antiplatelet,Inhibitor, Platelet,Inhibitor, Platelet Aggregation,PAR 1 Antagonists,Platelet Antagonist, Blood,Platelet Antiaggregant, Blood,Protease Activated Receptor 1 Antagonists
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000242 Cyclic AMP An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH. Adenosine Cyclic 3',5'-Monophosphate,Adenosine Cyclic 3,5 Monophosphate,Adenosine Cyclic Monophosphate,Adenosine Cyclic-3',5'-Monophosphate,Cyclic AMP, (R)-Isomer,Cyclic AMP, Disodium Salt,Cyclic AMP, Monoammonium Salt,Cyclic AMP, Monopotassium Salt,Cyclic AMP, Monosodium Salt,Cyclic AMP, Sodium Salt,3',5'-Monophosphate, Adenosine Cyclic,AMP, Cyclic,Adenosine Cyclic 3',5' Monophosphate,Cyclic 3',5'-Monophosphate, Adenosine,Cyclic Monophosphate, Adenosine,Cyclic-3',5'-Monophosphate, Adenosine,Monophosphate, Adenosine Cyclic
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults

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