Functional evidence for the rapid desensitization of 5-HT(3) receptors on vagal afferents mediating the Bezold-Jarisch reflex.
The aim of this study was to determine whether 5-hydroxytryptamine (5-HT)(3) receptors on cardiopulmonary afferents mediating the Bezold-Jarisch reflex (BJR) desensitize upon repeated exposure to selective agonists. BJR-mediated falls in heart rate, diastolic arterial blood pressure and cardiac output elicited by the 5-HT(3)-receptor agonists, phenylbiguanide (100 microg/kg, i.v.) or 2-methyl-5-HT (100 microg/kg, i.v.), progressively diminished upon repeated injection in conscious rats. The BJR responses elicited by 5-HT (40 microg/kg, i.v.) were markedly reduced in rats which had received the above injections of phenylbiguanide or 2-methyl-5-HT whereas the BJR responses elicited by L-S-nitrosocysteine (10 micromol/kg, i.v.) were similar before and after the injections of the 5-HT(3) receptor agonists. These findings suggest that tachyphylaxis to 5-HT(3) receptor agonists may be due to the desensitization of 5-HT(3) receptors on cardiopulmonary afferents rather than the impairment of the central or peripheral processing of the BJR.
Whalen
E J
EJ
Department of Pharmacology, The University of Iowa, Iowa City, IA 52242, USA.
Johnson
A K
AK
Lewis
S J
SJ
D000818:Animals; D002320:Cardiovascular Physiological Phenomena / Q000187:drug effects*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D044406:Receptors, Serotonin, 5-HT3; D012018:Reflex / Q000187:drug effects* / Q000502:physiology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D014630:Vagus Nerve / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D017366:Serotonin Receptor Agonists