CONTRIBUTION OF NEUROGENIC AND MYOGENIC FACTORS TO THE CONTRACTILE ACTIVITY OF THE GUINEA‐PIG DISTAL COLON IN VIVO AND IN VITRO

Publisher Website
Google Scholar
Abstract
The response of the guinea-pig distal colon to distension and drugs expected to interfere with neural control of contractile activity were investigated in urethane anaesthetized animals and compared to results obtained in the isolated preparation. Under urethane anaesthesia about 50% of the unloaded preparations had no detectable contractile activity. However these preparations contracted in response to topical acetylcholine. Saline distention induced the appearance of a phasic contractile activity in ''quiescent'' preparations and enhanced amplitude of contractions in previously active ones. Atropine (1 mg/kg i.v.) reduced tone and transiently suppressed phasic contractile activity of the distal colon. When phasic contractile activity resumed a second dose of atropine had no further inhibitory effect. Topical physostigmine (20 .mu.g in 0.1 ml) produced a marked and long lasting increase in tone paralleled by a marked enhancement in amplitude of the phasic contractile activity. These excitatory effects of topical physostigmine were suppressed by intravenous atropine (1 mg/kg). Hexamethonium (20 mg/kg i.v.) produced a sudden and transient increase in tone and suppressed DMPP (0.1 mg/kg i.v.) but not noradrenaline (2 .mu.g/kg i.v.) induced relaxations. Propranolol (2 mg/kg i.v.) or phentolamine (0.5 mg/kg i.v.) transiently increased tone of the guinea-pig distal colon and suppressed noradrenaline induced relaxations. DMPP induced relaxations were reduced by propranolol plus phentolamine. Topical tetrodotoxin (50 .mu.g in 0.1 ml) had an overall slight excitatory effect on phasic contractile activity of the in vivo preparation. The effects of i.v. atropine, hexamethonium, phentolamine or propranolol on tone and spontaneous activity were prevented by pretreatment with tetrodotoxin. Isolated segments of guinea-pig distal colon exhibited a fairly regular spontaneous phasic contractile activity whose amplitude was increased by stretching of the preparation. Atropine (3 .mu.M) produced a transient inhibition while hexamethonium (40 .mu.M) had no effect on spontaneous contractile activity. Tetrodotoxin (0.5 .mu.M) had both inhibitory and excitatory effects on tone and spontaneous activity of the preparation. At steady state amplitude of contractions was enhanced (15-30% increase) by tetrodotoxin. DMPP (1-100 .mu.M) first induced a phasic contraction and then suppressed transiently the spontaneous activity of the isolated preparation. DMPP-induced (100 .mu.M) contractions were abolished by either atropine or tetrodotoxin. DMPP-induced inhibition of the phasic contractile activity was almost unaffected by atropine (3 .mu.M) or phentolamine (0.5 .mu.M) plus propranolol (0.5 .mu.M) but almost suppressed by tetrodotoxin (0.5 .mu.M) suggesting activation of a non-adrenergic non-cholinergic (NANC) intramural mechanism. Hexamethonium (40 .mu.M) suppressed both the excitatory and the inhibitory effects of DMPP. Noradrenaline (1 .mu.M) suppressed transiently the phasic contractile activity of the guinea-pig isolated distal colon. The effect of noradrenaline was prevented by phentolamine (0.5 .mu.M) plus propranolol (0.5 .mu.M) but was unaffected by either hexamethonium (40 .mu.M) or tetrodotoxin (0.5 .mu.M). These findings provide evidence that at least three distinct types of innervation (cholinergic, sympathetic and NANC) modulate the myogenic (tetrodotoxin resistant) contractile activity of the guinea-pig distal colon. Moreover the in vivo model presented herein appears to be suitable for studying the interrelationship(s) existing between neurogenic and myogenic factors in regulating colonic motility in this species.