Renal hemodynamic responses to 5-hydroxytryptamine (5-HT): involvement of the 5-HT receptor subtypes in the canine kidney.
The study was designed to define the serotonin (5-HT) receptor subtypes in the canine kidney. An intrarenal infusion of 5-HT at a dose of 5 micrograms/min in anesthetized dogs resulted in a biphasic response of renal blood flow which decreased transiently then increased above the control level during prolonged infusion. The decrease of renal blood flow was abolished by infusion of methysergide but not by ketanserin, and the subsequent increase was abolished by infusion of either ketanserin or methysergide. Terazosin, an alpha1-adrenoceptor antagonist, did not modify the renal action of 5-HT. These findings suggest that the renal blood flow response induced by 5-HT did not depend on an indirect effect via the sympathetic nervous system, the initial vasoconstriction was mediated via a 5-HT1-like receptor, and that the latter vasodilatation was mediated via a 5-HT2 receptor. The infusion of 5-HT also increased urine flow and urinary excretion of sodium. These increases were reversed by pretreatment with ketanserin and abolished by methysergide. We propose that 5-HT may exert its antidiuretic action via a 5-HT1-like receptor in the tubules but that the renal hemodynamic changes induced by 5-HT may overcome its antidiuretic action. The present results suggest the existence of a 5-HT1-like and 5-HT2 receptor in the renal vasculature and a 5-HT1-like receptor in the renal tubules.
Shoji
T
T
Department of Pharmacology, Kagawa Medical School, Japan.
Tamaki
T
T
Fukui
K
K
Iwao
H
H
Abe
Y
Y
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D004285:Dogs; D005260:Female; D007650:Ketanserin / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism*; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D011224:Prazosin / Q000031:analogs & derivatives / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012079:Renal Circulation / Q000187:drug effects*; D012083:Renin / Q000097:blood; D012701:Serotonin / Q000494:pharmacology / Q000502:physiology*
D000317:Adrenergic alpha-Antagonists; D011985:Receptors, Serotonin; D012701:Serotonin; C041226:Terazosin; D007650:Ketanserin; D012083:Renin; D011224:Prazosin; D008784:Methysergide