A novel 5-HT1-like receptor subtype mediates cAMP synthesis in porcine pial vein.
The 5-hydroxytryptamine (5-HT) receptor subtype mediating 5-HT inhibition of spontaneous rhythmic contractions (SRC) in the porcine pial vein was characterized. Results from pharmacological studies using in vitro tissue bath techniques indicated that the inhibitory effects of 5-HT on SRC were qualitatively and quantitatively mimicked by 5-HT1-like agonists 5-methoxytryptamine (5-MT) and 5-carboxamidotryptamine (5-CT). 5-HT-, 5-MT-, and 5-CT-induced inhibitions of SRC were attenuated in a concentration-dependent manner by methysergide, which yielded similar pA2 values against these three agonists, suggesting that 5-HT, 5-MT, and 5-CT act on the same 5-HT1-like receptors. 5-MT inhibition of SRC was not affected by blocking 5-HT2 (with ketanserin and spiperone), 5-HT3 (with MDL-72222 and ICS-205-930), or 5-HT4 (with ICS-205-930) receptors. Neither was 5-MT inhibition of SRC affected by blocking 5-HT1A (with propranolol and spiperone), 5-HT1B (with propranolol), or 5-HT1C (with ketanserin) receptors. Furthermore, 5-HT and 5-MT inhibitions of SRC were enhanced by cilostazol [a selective adenosine 3',5'-cyclic monophosphate (cAMP) phosphodiesterase inhibitor] and were diminished by KT-5720 (a cAMP-dependent protein kinase inhibitor) but were not affected by M&B-22948 [a selective guanosine 3',5'-cyclic monophosphate (cGMP) phosphodiesterase inhibitor] or KT-5823 (a cGMP-dependent protein kinase inhibitor). Biochemical studies further demonstrated that 5-HT inhibition of SRC in porcine pial veins was accompanied by an increase in cAMP, but not cGMP, synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
Ueno
M
M
Department of Neurological Surgery, Wakayama Medical College, Japan.
Ishine
T
T
Lee
T J
TJ
D000818:Animals; D002550:Cerebral Veins / Q000378:metabolism*; D000242:Cyclic AMP / Q000096:biosynthesis*; D005260:Female; D008297:Male; D009712:Nucleotides, Cyclic / Q000502:physiology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010841:Pia Mater / Q000098:blood supply*; D047428:Protein Kinase Inhibitors; D011985:Receptors, Serotonin / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D013552:Swine
D009712:Nucleotides, Cyclic; D010726:Phosphodiesterase Inhibitors; D047428:Protein Kinase Inhibitors; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D012701:Serotonin; D000242:Cyclic AMP