Effect of atrial natriuretic factor and 8-bromo cyclic guanosine 3':5'-monophosphate on [3H]acetylcholine outflow from myenteric-plexus longitudinal muscle of the guinea pig.

We report that atrial natriuretic factor (ANF) inhibits electrically induced cholinergic twitches of longitudinal muscle in whole intestinal segments and myenteric-plexus longitudinal muscle (MPLM) strips from the guinea pig ileum. To elucidate the possible presynaptic mechanism of ANF's action, we studied spontaneous and stimulation-evoked radiolabeled acetylcholine (ACh) outflow from MPLM after incubation with [3H]choline. We developed a method of mounting and treating MPLM preparations, which allowed us, at the same time, to record isometric contractions and to determine [3H]ACh outflow upon electrical stimulation by a train of three pulses.

Inhibitory action of atrial natriuretic factor on cholinergic and nonadrenergic, noncholinergic neurotransmission in guinea pig small intestine.

We studied the effect of synthetic rat atrial natriuretic factor (ANF) (Ser 99-Tyr 126) on the isolated guinea pig proximal ileum. This preparation contained about one-third of the endogenous tissue ANF content which, for the most part, comes from the blood. ANF inhibited, in a dose-dependent manner, cholinergic twitch contractions (EC50 = 4.

Calcitonin gene-related peptide action on intestinal circular muscle.

Isolated segments of the guinea pig small intestine were used to examine the effect of calcitonin gene-related peptide (CGRP) on the motor activity of the circular muscle. CGRP (0.3-30 nM) initiated phasic contractions of the circular muscle due to stimulation of cholinergic neurons.

Action of histamine on nerve mediated responses of the guinea-pig ileum.

The effect of histamine on the responses of the guinea-pig ileum to stimulation of intramural nerves and to some potential nonadrenergic, noncholinergic (NANC) neurotransmitters was analysed. During sustained tonic histamine contraction, electrical stimulation of all intramural nerves elicited a biphasic response (contraction followed by after-relaxation) and application of ATP and bradykinin caused relaxation of the ileum in contrast to their contractile effect on basal tension. Histamine reduced contractile and augmented relaxatory NANC responses, and prevented capsaicin from producing any contractile effect and from significantly influencing the NANC contractions.

The effect of local anaesthetics on noncholinergic-nonadrenergic (NCNA) responses of the gut.

The newly synthesized carbamate local anaesthetics (heptacaine and BK-141) affected the NCNA responses of different segments of the guinea-pig small (jejunum, ileum) and large (colon, taenia coli) intestine in a similar manner to the classic local anaesthetics (procaine and trimecaine). The sensitivity of NCNA responses to the action of local anaesthetics was, in order: primary contraction greater than rebound contraction greater than primary relaxation. The action of the carbamate local anaesthetics resembled that of trimecaine more than that of procaine.

Effect of desensitization induced by adenosine 5'-triphosphate, substance P, bradykinin, serotonin, gamma-aminobutyric acid and endogenous noncholinergic-nonadrenergic transmitter in the guinea-pig ileum.

The cholinergic and noncholinergic-nonadrenergic (NCNA) excitatory and inhibitory responses of the guinea-pig ileum to transmural nerve stimulation (TNS) were studied. Unlike the contraction induced by histamine and acetylcholine the responses to TNS, ATP, substance P, bradykinin, 5-HT and GABA were not sustained. The contraction and its fading during TNS involved the activation of cholinergic, adrenergic and NCNA neurons.

Evidence that sensory neurons participate in the non-cholinergic, non-adrenergic contractile response of the guinea-pig ileum.

The possible role of non-cholinergic, non-adrenergic (NCNA) nerves in responses of the guinea-pig terminal ileum to transmural nerve stimulation (TNS) and that of sensory nerves in NCNA responses were investigated. The action of acetylcholine was almost abolished in the presence of histamine, whereas the contractions elicited by TNS were changed to frequency-dependent contraction followed by a secondary relaxation. Guanethidine did not alter the contractions or secondary relaxations.

The non-adrenergic non-cholinergic innervation and transmission in the small intestine.

An attempt has been made to summarize the present knowledge on the non-adrenergic non-cholinergic (NANC) transmission in the small intestine. The paper presents old and recent findings as well as the author's own results on the basic characteristics of the NANC mechanical and membrane potential changes. Further the sensitivity of NANC transmission to different influences, such as elevation or reduction of the muscle tension and membrane potential level, drug actions, desensitization of receptors, etc.

Role of Ca2+ in non-cholinergic, non-adrenergic responses to nerve stimulation of the guinea-pig small intestine.

The effects of calcium channel blockers (D-600, verapamil), sodium nitroprusside, papaverine, indomethacin, local anaesthetics and blockade of sodium pump activity on the non-cholinergic, non-adrenergic transmission in the guinea-pig duodenum, jejunum, proximal and terminal ileum were analysed in the presence of atropine and guanethidine. A decrease of the extracellular Ca2+ concentration inhibited the primary and rebound contractions but only in Ca2+ -free solution was the primary relaxation diminished. D-600, verapamil, sodium nitroprusside and papaverine inhibited both the primary and rebound contractions to the same degree and their effects on the primary relaxation were less pronounced than on the contractions.

Non-cholinergic, non-adrenergic responses to nerve stimulation of different regions of the guinea-pig small intestine.

Non-cholinergic, non-adrenergic responses to nerve stimulation recorded from smooth muscles of the guinea-pig duodenum, jejunum, proximal and terminal ileum were investigated in an attempt to characterize these responses. In the presence of atropine (1-2 mumol X l-1) and guanethidine (10 mumol X l-1) coaxial stimulation induced in all regions of the guinea-pig small intestine an initial relaxation (primary relaxation) upon which contraction (primary contraction) appeared, followed by rebound contraction. Noradrenaline decreased the cholinergic smooth muscle twitches, predominantly at low stimulation frequencies, and had a similar effect on the non-cholinergic, non-adrenergic primary relaxation, primary and rebound contractions.