ABSTRACT
Mechanical activity was recorded in circular and longitudinal smooth muscle preparations isolated from extensive regions of the porcine gastrointestinal tract in response to the FMRFamide-like neuropeptides F8Famide and A18Famide. In all preparations, the peptides were about equipotent in producing phasic contractions or enhancing spontaneous activity. The most prominent responses were observed in jejunal longitudinal strips which were on the average 91% (+/- 4% SEM, n = 15; 10(-6) M) of the histamine (10(-5) M) responses. The peptide-induced phasic activity was completely abolished by nifedipine but was unaffected by tetrodotoxin, atropine, phentolamine, yohimbine, phenoxybenzamine, propranolol, methysergide, cimetidine, indomethacin, levallorphane or naloxone. Both peptides enhanced acetylcholine-induced contractions. However, bovine ileum and guinea-pig taenia coli was not affected by these peptides. The results indicate that F8F- and A18F-amide contract porcine gastrointestinal smooth muscle by acting directly via non-opioid receptors on L-type calcium channels. In addition an increase of the sensitivity to cholinergic stimulation occurs.
Subject(s)
FMRFamide/pharmacology , Gastrointestinal Motility/drug effects , Neuropeptides/pharmacology , Oligopeptides/pharmacology , Animals , Calcium Channels/metabolism , Calcium Channels, L-Type , Enkephalin, Leucine/pharmacology , Enkephalin, Methionine/pharmacology , FMRFamide/analogs & derivatives , Histamine/pharmacology , In Vitro Techniques , Muscle Contraction/drug effects , Muscle, Smooth/drug effects , Muscle, Smooth/physiology , Neuropeptides/chemistry , Nifedipine/pharmacology , Nitroprusside/pharmacology , SwineABSTRACT
Mechanical activity was recorded in muscle preparations isolated from the human ileocaecal region. Gastrin-releasing peptide (GRP, 10(-9)-10(-7) mol L-1) produced two types of response in the different muscle layers. Longitudinally cut strips showed a concentration-dependent increase in the rhythmic activity, whereas the circularly orientated layers generally reacted with a small decrease in tone. These effects could not be influenced by blockade of adrenergic or cholinergic receptors or nerve blockade with tetrodotoxin (TTX). Application of pentagastrin did not mimic the action of GRP. These findings suggest a direct action of GRP on smooth muscle via distinct receptors which have already been demonstrated to exist in human gastrointestinal tract. The opposite effects on circular and longitudinal strips might indicate a modulatory role of GRP in the control of ileocolonic transit.
