Neural pathways and pharmacological modulation of defecation reflex in rats.
1. A new method was developed for quantitative studies on defecation reflex in urethane-anesthetized rats which involves the continuous infusion of saline (0.1 ml/min) to distend a balloon placed in the rectum. At threshold values, the balloon was expelled during an active rectal contraction. 2. Balloon expulsion was greatly delayed or even abolished by i.v. hexamethonium. Cord transection at the upper cervical level increased defecation threshold but a functional, hexamethonium-sensitive response was still elicited in spinal rats. 3. Various parameters of the defecation response were modulated by drugs (phentolamine, picrotoxin, naloxone) expected to interfere (either centrally or peripherally), with neural pathways controlling the autonomic outflow for the reflex response. 4. In capsaicin-pretreated rats (50 mg/kg s.c. on 2nd day of life, experiments performed at 2 months), daily fecal production was unchanged as compared to vehicle-treated, age-matched controls. However, under urethane-anesthesia, defecation threshold was increased at higher-than-normal values by capsaicin-pretreatment. 5. In in vitro experiments, capsaicin (1 microM) induced a transient inhibition of field stimulation-induced contractions of the rat isolated rectum. This effect was mimicked by application of calcitonin gene-related peptide (CGRP) (0.1 microM) while Substance P (0.1 microM) had an opposite effect. In preparations desensitized to exogenous CGRP, the inhibitory effect of capsaicin was almost abolished. 6. These findings indicate that in rats, reflex defecation is mainly organized at spinal level, although the participation of supraspinal centers may modify the functional response. Capsaicin-sensitive afferents may be involved in the initiation of certain forms of reflex defecation, although capsaicin-resistant mechanisms are capable of activating the normal excretory function.
Maggi
C A
CA
Pharmacology Department, A. Menarini Pharmaceuticals, Florence, Italy.
Giuliani
S
S
Santicioli
P
P
Patacchini
R
R
Meli
A
A
D000818:Animals; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin / Q000494:pharmacology; D003672:Defecation; D006584:Hexamethonium Compounds / Q000494:pharmacology; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009479:Neuropeptides / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012007:Rectum / Q000187:drug effects* / Q000294:innervation; D012018:Reflex / Q000187:drug effects*; D013373:Substance P / Q000494:pharmacology
D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin; D006584:Hexamethonium Compounds; D009270:Naloxone; D009479:Neuropeptides; D010646:Phentolamine; D010852:Picrotoxin; D013373:Substance P