Campus Access Only

All rights reserved. This publication is intended for use solely by faculty, students, and staff of University of the Pacific. No part of this publication may be reproduced, distributed, or transmitted in any form or by any means, now known or later developed, including but not limited to photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the author or the publisher.


Kinetic studies of the spasmogenic effects of serotonin and isolates from Byrsonima crassifolia leaves on rat fundus

Date of Award


Document Type

Dissertation - Pacific Access Restricted

Degree Name

Doctor of Philosophy (Ph.D.)

First Advisor

Marvin Malone


Leaf and bark extracts of a Mexican medicinal plant, Byrsonima crassifolia (Malpighiaceae), exhibited spasmogenic effects on isolated rat fundus and biphasic effects on jejunum and ileum. Preliminary evaluations using rat fundus in Krebs solution indicated that the activity of a 2% acetic acid extract of eaves (HOAcE) could be split into two types: (i) high-efficacy, low-potency, n-butanol-extracted, pargyline- and 1-(1-naphtylpiperazine) (1-NP)-sensitive, atropine-insensitive activity, and (ii) low-efficacy, high-potency, ethyl acetate-extracted, pargyline-insensitive, atropine- and 1-NP-sensitive activity. HOAcE lacked muscarinic and nicotinic effects on rat jejunum and frog rectus abdominis. Serotonin (5-HT) and HOAcE curves in fundus were parallel and 5-HT potency was 6,037 times that of HOAcE (95% confidence limits: 4,624-7,852). The pD$\sb2$ (affinity constant) for 5-HT was 7.96 (7.92-8.00) with pargyline added to the medium. 5-HT receptor-interaction kinetics using cholinergics and 5-HT agonists and antagonists was carried out. 1-NP competitively antagonized 5-HT. The 5-HT, antagonist s-(-)propranolol did not significantly antagonize 5-HT. The 5-HT$\sb2$ blocker ketanserin noncompetitively antagonized 5-HT and $\alpha$-Me-5-HT (pD$\sp\prime$2 = 5.6 and 6.7, respectively). The 5-HT$\sb3$ antagonist MDL-72222 inactivated only a small proportion of receptors (pD$\sp\prime$2 = 6.46). Atropine did not significantly modify the curve of 5-HT while fluoxetine noncompetitively antagonized 5-HT (pD$\sp\prime$2 = 5.8). 5-HT and $\alpha$-Me-5-HT curves were biphasic indicating two receptor interactions (high and low affinity). High-affinity pD$\sb2$ values for six different 5-HT agonists and 1-NP on rat fundus correlate well with reported rat brain (radioligand binding) pKd values at the 5-HT$\sb{\rm 1C}$ receptor (r = 0.94). Large scale extraction and fractionation of a methanol extract of leaves yielded two peaks of activity (Peak 1, lipophilic; Peak 2, polar). Peak 1 contained Compounds 1 to 7 (C1-C7); Peak 2 included C8-C15. Compound 1, C2, C3, C4, C10 and C11 were inactive while C8, C12 and C13 showed equivocal effects. Compound 5, C6, C7, C9, C14, C15, quercetin and gallic acid were active. Potencies were: C5 $>$ C6 $>$ C7 = quercetin $>$ C9 $>$ gallic acid. Efficacy (IA) was: C15 $\geq$ C14 $>$ gallic acid $>$ C9 $>$C5 $>$ C7 $>$ quercetin $>$ C6. Compound 9 and its aglycone quercetin were partial agonists (C9 IA = 70%, pD$\sb2$ = 6.35; quercetin IA = 60%, pD$\sb2$ = 6.58). Compound 9 noncompetitively antagonized 5-HT (pD$\sp\prime$2 = 6.10), while quercetin did not. Compound 14 and C15, the most active compounds, had similar response curves but these curves were not parallel to 5-HT. Spasmogenic ED$\sb{50}$ values for C14 = 0.76 (0.38-1.54) $\mu$g/mL and C15 = 0.76 (0.41-1.42) $\mu$g/mL. Gram for gram 5-GT was 181 $\times$ C14 and 182 $\times$ C15.



This document is currently not available here.

To access this thesis/dissertation you must have a valid email address and log-in to Scholarly Commons.

Find in PacificSearch Find in ProQuest



If you are the author and would like to grant permission to make your work openly accessible, please email