BIOMAT Database Logo BIOMAT Database Logo

Pharmacological studies on the inhibitory action of melatonin and putative melatonin analogues on porcine vascular smooth muscle. 2000

N Ting, and A Thambyraja, and D Sugden, and E Scalbert, and P Delagrange, and V G Wilson
School of Biomedical Sciences, Queen's Medical School, University of Nottingham, UK.

The effect of high concentrations of melatonin, and related indole-based and naphthalene-based derivatives, has been examined in the porcine coronary artery, pulmonary artery and the marginal artery of the colon. In addition, we have pharmacologically examined the role of cyclic GMP in the relaxatory action of these agents. Cumulative addition of melatonin (3-300 microM) caused a slowly developing relaxation in all three vascular preparations pre-contracted with 9,11-dideoxy-9a,11a-methanoepoxy prostaglandin F2alpha (U46619), a thromboxane mimetic agent. The estimated pIC50 values were 4.10-3.70 (coronary artery), 3.89 (pulmonary artery) and 3.96 (marginal artery). All melatonin analogues examined also produced concentration-dependent inhibition of U46619-induced contractions of the coronary and marginal arteries in a qualitatively similar manner to melatonin. The rank order of potency (based on the pIC50 values) of these compounds in both vascular tissues was N-[2-(3-ethyl-7-methoxynaphthyl) ethyl]-acetamide (S21634) >2-iodomelatonin = N-[2-(7-methoxynaphth-1-yl)-ethyl]-acetamide (S20098) = N-[2-naphth-1-yl-ethyl]-cyclobutyl carboxamide (S20928) >melatonin >N-acetyl-5-HT. Finally, the pharmacological characteristics of melatonin and S21634 as phosphodiesterase inhibitors were compared to those of zaprinast, a known cyclic GMP-specific phosphodiesterase inhibitor. Zaprinast also caused concentration-dependent inhibition of U46619-induced tone. All three compounds, zaprinast (10 microM), melatonin (300 microM) and S21634 (30 microM), significantly enhanced sodium nitroprusside-induced relaxations. The inhibitory action of zaprinast per se was greater in the presence of the endothelium and significantly attenuated by 3 microM 1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one (ODQ), a selective inhibitor of guanylyl cyclase. In marked contrast, the vasorelaxant action of melatonin and S21634 was not affected by the removal of the endothelium or the addition of ODQ. In summary, we have shown that porcine arterial smooth muscle relaxes in response to high concentrations of melatonin and other related melatonin receptor ligands. However, it appears that the receptive site is pharmacologically different from the melatonin receptors currently known and does not involve inhibition of cyclic GMP-specific phosphodiesterase.

UI MeSH Term Description Entries
D008550 Melatonin A biogenic amine that is found in animals and plants. In mammals, melatonin is produced by the PINEAL GLAND. Its secretion increases in darkness and decreases during exposure to light. Melatonin is implicated in the regulation of SLEEP, mood, and REPRODUCTION. Melatonin is also an effective antioxidant.
D009131 Muscle, Smooth, Vascular The nonstriated involuntary muscle tissue of blood vessels. Vascular Smooth Muscle,Muscle, Vascular Smooth,Muscles, Vascular Smooth,Smooth Muscle, Vascular,Smooth Muscles, Vascular,Vascular Smooth Muscles
D011651 Pulmonary Artery The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. Arteries, Pulmonary,Artery, Pulmonary,Pulmonary Arteries
D003331 Coronary Vessels The veins and arteries of the HEART. Coronary Arteries,Sinus Node Artery,Coronary Veins,Arteries, Coronary,Arteries, Sinus Node,Artery, Coronary,Artery, Sinus Node,Coronary Artery,Coronary Vein,Coronary Vessel,Sinus Node Arteries,Vein, Coronary,Veins, Coronary,Vessel, Coronary,Vessels, Coronary
D004347 Drug Interactions The action of a drug that may affect the activity, metabolism, or toxicity of another drug. Drug Interaction,Interaction, Drug,Interactions, Drug
D004730 Endothelium, Vascular Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components. Capillary Endothelium,Vascular Endothelium,Capillary Endotheliums,Endothelium, Capillary,Endotheliums, Capillary,Endotheliums, Vascular,Vascular Endotheliums
D006152 Cyclic GMP Guanosine cyclic 3',5'-(hydrogen phosphate). A guanine nucleotide containing one phosphate group which is esterified to the sugar moiety in both the 3'- and 5'-positions. It is a cellular regulatory agent and has been described as a second messenger. Its levels increase in response to a variety of hormones, including acetylcholine, insulin, and oxytocin and it has been found to activate specific protein kinases. (From Merck Index, 11th ed) Guanosine Cyclic 3',5'-Monophosphate,Guanosine Cyclic 3,5 Monophosphate,Guanosine Cyclic Monophosphate,Guanosine Cyclic-3',5'-Monophosphate,3',5'-Monophosphate, Guanosine Cyclic,Cyclic 3',5'-Monophosphate, Guanosine,Cyclic Monophosphate, Guanosine,Cyclic-3',5'-Monophosphate, Guanosine,GMP, Cyclic,Guanosine Cyclic 3',5' Monophosphate,Monophosphate, Guanosine Cyclic
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000927 Anticonvulsants Drugs used to prevent SEIZURES or reduce their severity. Anticonvulsant,Anticonvulsant Drug,Anticonvulsive Agent,Anticonvulsive Drug,Antiepileptic,Antiepileptic Agent,Antiepileptic Agents,Antiepileptic Drug,Anticonvulsant Drugs,Anticonvulsive Agents,Anticonvulsive Drugs,Antiepileptic Drugs,Antiepileptics,Agent, Anticonvulsive,Agent, Antiepileptic,Agents, Anticonvulsive,Agents, Antiepileptic,Drug, Anticonvulsant,Drug, Anticonvulsive,Drug, Antiepileptic,Drugs, Anticonvulsant,Drugs, Anticonvulsive,Drugs, Antiepileptic
D013552 Swine Any of various animals that constitute the family Suidae and comprise stout-bodied, short-legged omnivorous mammals with thick skin, usually covered with coarse bristles, a rather long mobile snout, and small tail. Included are the genera Babyrousa, Phacochoerus (wart hogs), and Sus, the latter containing the domestic pig (see SUS SCROFA). Phacochoerus,Pigs,Suidae,Warthogs,Wart Hogs,Hog, Wart,Hogs, Wart,Wart Hog

Related Publications

N Ting, and A Thambyraja, and D Sugden, and E Scalbert, and P Delagrange, and V G Wilson
[Pharmacological studies of the action of cetiedile on smooth muscle].
February 1978, Bollettino della Societa italiana di biologia sperimentale,
N Ting, and A Thambyraja, and D Sugden, and E Scalbert, and P Delagrange, and V G Wilson
The mechanism of inhibitory action of diltiazem on vascular smooth muscle contractility.
August 1981, The Journal of pharmacology and experimental therapeutics,
N Ting, and A Thambyraja, and D Sugden, and E Scalbert, and P Delagrange, and V G Wilson
Melatonin modulates vascular smooth muscle tone.
December 1997, Journal of biological rhythms,
N Ting, and A Thambyraja, and D Sugden, and E Scalbert, and P Delagrange, and V G Wilson
[Inhibitory action of protamine and lanthanum on the smooth muscle].
November 1973, Nihon yakurigaku zasshi. Folia pharmacologica Japonica,
N Ting, and A Thambyraja, and D Sugden, and E Scalbert, and P Delagrange, and V G Wilson
Inhibitory action of formamide on smooth muscle contraction.
September 1968, Life sciences,
N Ting, and A Thambyraja, and D Sugden, and E Scalbert, and P Delagrange, and V G Wilson
[Inhibitory action of 1,3,5-trimethoxybenzene on smooth muscle].
November 1962, Comptes rendus hebdomadaires des seances de l'Academie des sciences,
N Ting, and A Thambyraja, and D Sugden, and E Scalbert, and P Delagrange, and V G Wilson
The inhibitory action of melatonin on the contractile response to 5-hydroxytryptamine in various isolated vascular smooth muscles.
January 1986, General pharmacology,
N Ting, and A Thambyraja, and D Sugden, and E Scalbert, and P Delagrange, and V G Wilson
[Pharmacological studies on drugs affecting smooth muscle].
July 1968, Nihon yakurigaku zasshi. Folia pharmacologica Japonica,
N Ting, and A Thambyraja, and D Sugden, and E Scalbert, and P Delagrange, and V G Wilson
Inhibitory action of norepinephrine on sodium transport in vascular smooth muscle cells in culture.
March 1989, Pflugers Archiv : European journal of physiology,
N Ting, and A Thambyraja, and D Sugden, and E Scalbert, and P Delagrange, and V G Wilson
Studies on the mechanism of the inhibitory effect of desipramine (DMI) on vascular smooth muscle contraction.
June 1970, The Journal of pharmacology and experimental therapeutics,
Copied contents to your clipboard!