Further characterization of the 5-HT receptor mediating vascular relaxation and elevation of cyclic AMP in porcine isolated vena cava.
1. 5-Hydroxytryptamine (5-HT) and 5-carboxamidotryptamine (5-CT) produce both smooth muscle relaxation and elevation of tissue adenosine 3':5'-cyclic monophosphate (cyclic AMP) levels in isolated rings of neonatal porcine vena cava. We now present studies attempting to characterize in more detail the 5-HT receptor mediating these responses. 2. Both 5-HT and 5-CT relaxed porcine isolated vena cava rings (EC50 values 200 nM and 4 nM respectively) and elevated tissue cyclic AMP levels (EC50 values 1500 nM and 16 nM respectively). For both responses 5-CT was approximately 50-100 fold more potent than 5-HT. 3. Both 5-CT-induced smooth muscle relaxation and cyclic AMP elevation were potently and specifically antagonized to a similar extent by methiothepin, methysergide and spiperone. 4. At concentrations up to 1 microM, 8-hydroxy-2-(di-n-propylamino) tetralin, buspirone, ipsapirone, n,n-dipropyl-5-CT, cyanopindolol, RU24969, ketanserin, GR38032 and GR43175 were devoid of both agonist and antagonist activity for both responses. 5. These findings suggest that the same 5-HT1-like receptor mediates both smooth muscle relaxation and elevation of cyclic AMP. This receptor is unlike any known 5-HT1 ligand binding site or adenylate cyclase-coupled 5-HT receptor in brain tissues.
Sumner
M J
MJ
Pharmacology Division, Glaxo Group Research, Hertfordshire.
Feniuk
W
W
Humphrey
P P
PP
D000818:Animals; D000831:Animals, Newborn; D000242:Cyclic AMP / Q000378:metabolism*; D066298:In Vitro Techniques; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000031:analogs & derivatives; D013552:Swine; D014683:Vena Cava, Superior / Q000187:drug effects / Q000378:metabolism
D011985:Receptors, Serotonin; D012701:Serotonin; C047087:5-carboxamidotryptamine; D000242:Cyclic AMP