5-Hydroxytryptamine1D-like receptors mediate contraction of partially depolarized rabbit renal arteries.
This study characterizes the 5-hydroxytryptamine (5-HT) receptors involved in the contraction of rabbit renal arteries which had been previously precontracted submaximally by partial depolarization. In the presence of ketanserin (10(-6) M) to block 5-HT2 receptors, 5-HT, 5-carboxamido-tryptamine (5-CT) and other 5-HT receptor agonists caused contraction of partially depolarized (22 mM KCl) rabbit renal arteries whereas they were without effect in quiescent tissues (4.7 mM KCl). 5-CT was the most potent agent tested, producing concentration-related increases in tension over the range of 10(-9) to 10(-6) M, attaining 44 +/- 2% of the tissue maximum with a EC50 of 4.8 +/- 0.9 x 10(-8) M. The relative order of agonist potency in partially depolarized tissues was 5-CT > 5-HT > 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H indole > or = sumatriptan > 8-hydroxy-2-(di-n-propyl-amino)tetralin > cisapride. Responses to 5-CT and sumatriptan were antagonized in a concentration-dependent fashion by methiothepin (3 x 10(-8)-3 x 10(-7) M). In the case of 5-CT, Schild analysis showed that this antagonism was competitive, giving a pA2 value of 7.72. Rauwolsine (3 x 10(-7)-10(-6) M) and metergoline (10(-6) M) also produced modest antagonism of 5-CT and sumatriptan-induced responses. With sumatriptan as agonist, rauwolscine gave a pKB of 6.43, however its antagonism of 5-CT appeared noncompetitive because it was associated with a reduction in maximum response (pKB' = 6.54).(ABSTRACT TRUNCATED AT 250 WORDS)
Choppin
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Synthélabo Recherche, Department of Biology, Bagneux, France.
O'Connor
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D000818:Animals; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000502:physiology; D011817:Rabbits; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012077:Renal Artery / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin