Contribution of neurogenic and myogenic factors to the contractile activity of the guinea-pig distal colon in vivo and in vitro

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 bout 50% of the unloaded preparations had no detectable contractile activity. However these preparations contracted in response to topical acetylcholine. Saline distension 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 micrograms 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 micrograms/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 micrograms 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 microM) produced a transient inhibition while hexamethonium (40 microM) had no effect on spontaneous contractile activity. Tetrodotoxin (0.5 microM) 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 microM) first induced a phasic contraction and then suppressed transiently the spontaneous activity of the isolated preparation.(ABSTRACT TRUNCATED AT 400 WORDS)