Irving Goodman

Coherin: A New Peptide of the Bovine Neurohypophysis with Activity on Gastrointestinal Motility

A factor with potent activity in the regulation of mammalian gastrointestinal motor function has been isolated from the bovine posterior pituitary gland by a process allowing minimal dissociation of neurophysin-bound complexes and the separation of free unbound peptides. This substance alters the frequency, amplitude, rhythm, and duration of peristaltic contraction.

Chemical factors affecting spontaneous motility of the small intestine in the rat—1: Sulfhydryl reactants

Abstract To determine whether the sulfhydryl group is involved in the mechanism of intestinal smooth muscle contractility, relative reactivities of a variety of sulfhydryl reactants with the cysteine sulfhydryl group were evaluated by a modification of the indophenol method (Basford and Huennekens 10 ) along with parallel studies of the effects of the same sulfhydryl reactants on spontaneous motility and response to acetylcholine of isolated segments of rat ileum in Ringers solution. Characteristics of intestinal contractility of normal and treated segments were continuously recorded on a photometric apparatus devised to measure frequency and amplitude of isotonic contractions. Compounds highly reactive toward the sulfhydryl group included the following : lead acetate, zinc chloride, cadmium chloride, p -hydroxymercuribenzoic acid, 2-iodoacetamide, 2,4-dinitrofluorobenzene, hydrogen peroxide, iodine in potassium iodide, alloxan, N-ethylmaleimide, patulin, N-phenylmaleimide. These were compared with a number of compounds which do not react with the SH group including: urea, sorbitol hydrate, inosine, sucrose, lecithin, and glycyl- l -serine. Results of this study demonstrate that reagents of widely varied structures but with high reactivity toward the SH group profoundly affect the spontaneous motility of the isolated small intestine of the rat. Curves are given to illustrate the decrease in energy of acetylcholine-induced contraction with increased concentrations of sulfhydryl reactants. Representative traces of individual experiments demonstrating normal motility and the inhibitory effects of sulfhydryl reactants are given. In all cases studied compounds showing high reactivity toward the SH group, at appropriate concentrations (10 −2 to 10 5 M) can completely inhibit spontaneous motility of the small intestine; all can block the acetylcholine-induced contraction. Many at appropriate concentrations (10 −4 to 10 −7 M) can induce contraction.

The physiologic properties and therapeutic potential of coherin

Coherin, a peptide isolated from the bovine neurohypophysis, has been shown to be an effective therapeutic agent in post-gastric surgery physiologic obstruction and regional ileitis. Of twenty-four patients with post-gastric surgery physiologic obstruction, coherin relieved symptoms in twenty-three, a 96 per cent efficacy rate. The efficacy of coherin with ileitis was based on the fact that ten of twenty-seven patients treated have required coherin on a continuing basis to stay functional. These patients have requested coherin treatment for an average of five years each, and have each on multiple occasions tried to discontinue coherin treatment with prompt return of symptoms and cessation of symptoms when coherin was reinstituted. All of the ileitis patients had previously failed to respond to standard and usual medical treatment.

The effect of coherin on the basic electrical rhythm of the dog ileumin vivo

Coherin, a substance isolated from the bovine posterior pituitary gland exists as a complex which is dissociated to yield at least two distinct enteroactive polypeptides, coherin A and B, and a third having little or no activity, coherin C. The effects of intravenous injection of nondissociated coherin (coherin G-25), coherin A, coherin B, vasopressin, and normal saline solution on the BER of the ileal Biebl loop in fasting dogs were investigated. The BER patterns in preinjection and postinjection periods were compared for each substance. The effects on the BER of each substance were compared with that of saline. Monopolar recordings were made from six electrodes 5 mm apart inserted into the ileal musculature of the Biebl loops. Coherin A significantly altered the electroenterograms in two ways. It increased phase locking in the ileal BER of the fasting dog and increased the amount of caudad BER propagation.

On the synthesis and identification of the epinephrin metabolite 4-hydroxy-3-methoxy-dl-mandelic acid

Abstract An improved synthesis of the epinephrin metabolite, 4-hydroxy-3-methoxy- dl -madelic acid (HMMA), is described starting with 2-methoxyphenol and glyoxylic acid. The azo dyes derived from HMMA by condensation with the diazonium salts of p -nitroaniline and of sulphanilic acid have been prepared and characterized and are shown to be identical with the corresponding azo dyes derived from 2-methoxyphenol. The elimination of an oxyacetic acid group from HMMA occurs in the course of azo dye formation and may lead to ambiguities in the identification and quantitation of HMMA and other phenolic compounds in biological materials.

Intestinal motility: I. Control mechanisms in the basic electric rhythm of the canine small intestine

Abstract The pacesetter potential of the BER in the fasting dog has a varied rapidly changeable pattern. A polypeptide extractable from the posterior pituitary when given intravenously has the capacity to alter the varied pacesetter potential pattern in the fasting dog to that of a highly organized cephalocaudad coherent pattern. Serotonin when instilled intraluminally in a dog pretreated with iv Coherin has the capacity of making the pacesetter potentials simultaneous in a particular segment of small intestine. This observable pacesetter potential performance would seem to preclude an anatomically stable focal pacemaker apparatus. An alternative model is proposed comprised of a linear intramural pacing apparatus demonstrable in the form of an electropositive beat and involving varying lengths of intestine depending on physiological stimulus.

Protein binding of coherin and other small molecules by thin-layer gel chromatography

The protein binding stoichiometry of small molecules is here determined on a nanomole scale by a simplified procedure utilizing chromatography on thin layers of cross-linked dextran gels. New data are presented on the thin layer chromatographic properties of representative ligands, including a-amino acids, peptides, dyes and fluorigenic reagents, in relation to their molecular weights, polar characteristics, gel water regain values and denaturants, providing criteria for the general application of this method to studies of ligand binding with large as well as small molecules. By this procedure coherin peptides, A1 and B1--4, respectively, bind to coherin C in the molar ratio, 2:1, with a binding constant of about 10(5) M-1. Coherin C is believed to act as a carrier peptide.

Intestinal motility. II. Electro-motor correlations in the canine small intestine.

Abstract The capacity to produce simultaneous pacesetter potentials that are correlated with rhythmic mass spasms over the entire segment of a Biebl loop has by special recording techniques demonstrated the following: In the hypermotile state the intestinal musculature is active throughout each electrical cycle of the BER. The longitudinal muscle contracts just before or at the origin of the pacesetter potentials and terminates just prior to the midpoint between pacesetter potentials. The circular muscle immediately follows and contracts just prior to the midpoint between pacesetter potentials and terminates before the next pacesetter potentials.