Central administration of 5-HT activates 5-HT1A receptors to cause sympathoexcitation and 5-HT2/5-HT1C receptors to release vasopressin in anaesthetized rats.

Abstract

1. The effects of intracerebroventricular injections to the right lateral ventricle (i.c.v.) of 5-hydroxytryptamine (5-HT, 40 and 120 nmol kg-1), N,N-di-n-propyl-5-carboxamidotryptamine (DP-5-CT; 3 nmol kg-1), 5-carboxamidotryptamine (5-CT; 3 nmol kg-1), 8-hydroxy-2-(di-N-propylamino) tetralin (8-OH-DPAT; 3, 40 and 120 nmol kg-1) and 1-(2,5-di-methoxy-4-iodophenyl)-2-aminopropane (DOI; 40 and 120 nmol kg-1) on renal sympathetic nerve activity, blood pressure, heart rate and phrenic nerve activity were investigated in normotensive rats anaesthetized with alpha-chloralose. 2. 5-HT caused a long lasting pressor response which was associated with an initial bradycardia and renal sympathoinhibition followed by a tachycardia and renal sympathoexcitation. Pretreatment with the 5-HT2/5-HT1C receptor antagonists, cinanserin (300 nmol kg-1, i.c.v.) or LY 53857 (300 nmol kg-1, i.c.v.) reversed the initial bradycardia and sympathoinhibition to tachycardia and sympathoexcitation. Combined pretreatment with LY 53857 (300 nmol kg-1, i.c.v.) and the 5-HT1A antagonist, spiroxatrine (300 nmol kg-1, i.c.v.), blocked the effects of 5-HT on all the above variables. 3. Pretreatment with the vasopressin V1-receptor antagonist, beta-mercapto-beta,beta-cyclopentamethylene-propionyl1, O-Me-Tyr2, Arg8-vasopressin [(d(CH2)5Tyr(Me)AVP, 10 micrograms kg-1, i.v.] did not affect the magnitude but reduced the duration of the pressor response produced by i.c.v. 5-HT and reversed the initial bradycardia and renal sympathoinhibition to tachycardia and sympathoexcitation. 4. 1-(2,5-Di-methoxy-4-iodophenyl)-2-aminopropane (DOI) caused a pressor effect which was associated with a bradycardia and sympathoinhibition. These effects were blocked by pretreatment with BWSOlC67 (0.1 mg kg-', i.v.), a peripherally acting 5-HT2/5-HTc receptor antagonist. However,BWSOlC67 (0.1 mg kg-', i.v.) failed to block the effects of i.c.v. 5-HT.5. DP-5-CT, 5-CT and 8-OH-DPAT (3 nmol kg-', i.c.v.) caused sympathoexcitation, tachycardia and a rise in blood pressure. Pretreatment with methiothepin (1 mg kg-', i.v.) or spiroxatrine (300 nmol kg-',i.c.v.) attenuated the response to i.c.v. DP-5-CT.6. It is concluded that i.c.v. administration of 5-HT activates 5-HTlA receptors to cause sympathoexcitation and 5-HT2 or 5-HT1c receptors to cause the release of vasopressin.

• Authors: I K Anderson, G R Martin, A G Ramage
• Journal: British journal of pharmacology (Br J Pharmacol) Vol. 107 Issue 4 Pg. 1020-8 (Dec 1992) ISSN: 0007-1188 [Print] England
• PMID: 1467825 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Dioxanes
• Receptors, Serotonin
• Receptors, Vasopressin
• Serotonin Antagonists
• Serotonin Receptor Agonists
• Spiro Compounds
• Tryptamines
• Vasopressins
• Serotonin
• N,N-dipropylcarboxamidotryptamine
• spiroxatrine

Topics

• Animals
• Blood Pressure (drug effects)
• Dioxanes (pharmacology)
• Heart Rate (drug effects)
• Injections, Intraventricular
• Kidney (innervation)
• Male
• Phrenic Nerve (drug effects, physiology)
• Rats
• Rats, Sprague-Dawley
• Receptors, Serotonin (drug effects, metabolism)
• Receptors, Vasopressin (drug effects)
• Serotonin (administration & dosage, pharmacology)
• Serotonin Antagonists (pharmacology)
• Serotonin Receptor Agonists (pharmacology)
• Spiro Compounds (pharmacology)
• Sympathetic Nervous System (drug effects, physiology)
• Tryptamines (administration & dosage, pharmacology)
• Vasopressins (metabolism)