Antiproliferative effects of the serotonin type 2 receptor antagonist, ketanserin, on smooth muscle cell growth in rats

Journal Article · Mon Dec 31 23:00:00 EST 1990 · Journal of Cardiovascular Pharmacology; (United States)

DOI:https://doi.org/10.1097/00005344-199117002-00038· OSTI ID:5080442

Uehara, Y; Nagata, T; Matsuoka, H; Numabe, A; Hirawa, N; Takada, S; Ishimitsu, T; Yagi, S; Sugimoto, T ^[1]

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1. 2nd Department of Medicine, University of Tokyo (Japan)

The authors defined the role of a serotonin type 2 receptor antagonist, ketanserin, in the growth of aortic vascular smooth muscle cells (VSMCs) from Wistar rats, using cell culture and cell synchrony methods. Deoxyribonucleic acid (DNA) replication in the G0/G1- or G1/S-synchronized VSMCs was assessed by (3H)thymidine uptake into DNA. Ketanserin at 2 {times} 10(-5) M significantly decreased the thymidine uptake by 48% in the proliferating VSMCs, whereas methysergide, a nonspecific serotonin inhibitor, unaffected the thymidine uptake. Ketanserin at 10(-5) M did not influence the duration of the G1 resting period. However, this dose of ketanserin significantly lowered DNA replication in the DNA synthetic (S) period in a dose-dependent manner. Neither methysergide nor the alpha 1-adrenoceptor antagonist, prazosin, affected DNA synthesis in the S period. Ketanserin exhibits antiproliferative effects on rat VSMC growth probably through the suppression of DNA replication in the S phase. This property would also contribute to the vascular protective effects of ketanserin with its well-documented antihypertensive action.

• OSTI ID: 5080442
• Journal Information: Journal of Cardiovascular Pharmacology; (United States), Journal Name: Journal of Cardiovascular Pharmacology; (United States) Vol. 17 Suppl 2; ISSN 0160-2246; ISSN JCPCD
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINES
ANIMAL CELLS
ANIMALS
AORTA
AROMATICS
ARTERIES
AUTONOMIC NERVOUS SYSTEM AGENTS
AZAARENES
AZINES
AZOLES
BIOLOGICAL FUNCTIONS
BLOOD VESSELS
BODY
CARDIOVASCULAR SYSTEM
CELL PROLIFERATION
DNA
DNA REPLICATION
DRUGS
ENZYME INHIBITORS
HETEROCYCLIC COMPOUNDS
HYDROGEN COMPOUNDS
HYDROXY COMPOUNDS
INDOLES
ISOTOPE APPLICATIONS
MAMMALS
MEMBRANE PROTEINS
MUSCLES
NEUROREGULATORS
NUCLEIC ACID REPLICATION
NUCLEIC ACIDS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PROTEINS
PYRIMIDINES
PYRROLES
RADIOPROTECTIVE SUBSTANCES
RATS
RECEPTORS
RIBOSIDES
RODENTS
SEROTONIN
SYMPATHOMIMETICS
THYMIDINE
TRACER TECHNIQUES
TRITIUM COMPOUNDS
TRYPTAMINES
VERTEBRATES