Korean J Physiol Pharmacol.
1997 Jun;1(3):315-323.
Renal functional responses to a centrally-administered 5-HT-1A agonist in the anesthetized rabbits
- Affiliations
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- 1Department of Pharmacology, Medical School, Chonnam National University, Kwangju 501-190, Korea.
- 2Institute of Medical Sciences, Medical School, Chonnam National University, Kwangju 501-190, Korea.
- 33Department of Pharmacology, Dental School, Chonnam National University, Kwangju 501-190, Korea.
Abstract
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Central tryptaminergic system has been shown to play an important role
in the regulation of renal function: 5-HT-1 (5-hydroxytryptamine-1)
receptors might seem to mediate the diuresis and natriuresis, whereas
the 5-HT-2 and 5-HT-3 receptors mediate the antidiuretic and
antinatriuretic effects. This study attempted to delineate the role of
central 5-HT-1A subtype in the regulation of rabbit renal function by
observing the renal effects of
intracerebroventricularly(icv)-administered PAPP
(p-aminophenylethyl-m-trifluoromethylphenyl piperazine, LY165163), a
selective agonist of 5-HT-1A receptors. PAPP in doses ranging from 40
to 350 microgram/kg icv induced significantly diuresis, natriuresis, and
kaliuresis, along with increased renal perfusion and glomerular
filtration. Systemic blood pressure was also increased. Free water
reabsorption (T-cH-2O), a measure of ADH (antidiuretic hormone)
secretion, was increased also. Intravenous 350 microgram/kg of PAPP elicited
antidiuresis and antinatriuresis together with decreased blood
pressure, thus indicating that the effects of icv PAPP were brought
about through the central mechanisms, not by direct peripheral effects
of the drug on kidney. Ketanserin, a selective 5-HT-2 antagonist, 40
microgram/kg icv, did not affect the renal effects of the icv PAPP.
Methysergide, a non-selective 5-HT-1 antagonist, also did not block the
renal functional responses by the icv PAPP. NAN-190, a 5-HT-1A
antagonist, also did not antagonized the renal action of the icv PAPP.
However the increased free water reabsorption was abolished by both
methysergide or ketanserin pretreatment. The increments of blood
pressure by icv PAPP was blocked only by NAN-190 pretreatment. These
observations
suggest that the central 5-HT-1A receptor might be involved in the central regulation of rabbit renal function by exerting the diuretic and natriuretic influences.
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