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R J Miller

Publications and source records attributed to R J Miller.

At least 343 records · Page 19Linked to original sources
PubMed1983

Regulation of serotonin release from rabbit intestinal enterochromaffin cells.

Serotonin release from rabbit enterochromaffin cells located in the mucosal epithelium of the small intestine was studied in vitro. Serotonin release from both the serosal and mucosal sides of the small intestine was measured. The addition of muscarinic but not nicotinic cholinergic agonists to the serosal medium resulted in a large but transient increase in serotonin release from the serosal but not the mucosal side of the intestine. Mucosal addition of these agents was ineffective. Serotonin release stimulated by the cholinergic agonist carbachol appeared to be dependent upon influx of extracellular Ca++ for the following reasons: 1) depletion of serosal Ca++ inhibited carbachol-stimulated release; 2) carbachol-stimulated serotonin release was blocked by the inorganic calcium channel blockers Co++, Ni++, Cd++, La and Gd; and 3) serosal serotonin release was increased by the Ca++ ionophore, ionomycin, and by Ba++. The addition of 8-bromoadenosine cyclic AMP or the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine, to the serosal medium produced a sustained elevation of serosal serotonin release. 8-bromoadenosine-cyclic AMP-stimulated release was not blocked by depleting extracellular Ca++. Forskolin, a compound which stimulates adenylate cyclase, also stimulated serosal serotonin release. 8-bromoadenosine-cGMP had no effect on serotonin release. Somatostatin (10(-8)-10(-6) M) caused a dose-dependent inhibition of carbachol-stimulated serotonin release. Somatostatin (10(-6) M) only partially inhibited serotonin release stimulated by 8-bromoadenosine-cyclic AMP, 3-isobutyl-1-methylxanthine and forskolin and had no effect on release stimulated by Ba++. The results suggest potential roles for both calcium and cyclic nucleotides in the regulation of serotonin release.

Animals↗
PubMed1983

[3H]ethylketocyclazocine binding to NCB-20 hybrid neurotumor cells.

Ethylketocyclazocine (EKC) binds to two sites on NCB-20 neuroblastoma X Chinese hamster brain hybrid cells (KDH = 2 nM, Bmax = 21,000 sites/cell; KDL = 27 nM, Bmax = 140,000 sites/cell. The high-affinity site has been characterized as a delta opiate receptor. The low-affinity site is relatively benzomorphan-specific; opioid peptides, morphine, etorphine, and naloxone do not compete at it. Rank order of potency among benzomorphans is (+)-EKC greater than Mr 2267 greater than (+)-ketocyclazocine greater than (+)-SKF 10047 greater than bremazocine greater than cyclazocine. Among other drugs of interest that inhibit [3H]EKC binding are phencyclidine and its analogues, Ki values for which are 0.2-40 microM. Stereoselectivity is the reverse of other opioid receptors: (+)-EKC much much greater than (-)-EKC, Mr 2267 greater than Mr 2266, (+)-SKF 10047 greater than (-)-SKF 10047. The site is sensitive to trypsin, but not to N-ethylmaleimide. Binding is insensitive to nucleotides, slightly sensitive to physiological concentrations of sodium, magnesium, and manganese ions and to EDTA but not EGTA.

Animals↗
PubMed1983

The geriatric bunion: correction of metatarsus primus varus and hallux valgus with the Swanson total joint implant.

The authors have evaluated the long-term results of the Keller/Mayo bunionectomy with replacement of the first metatarsophalangeal joint with a Silastic double-stemmed implant (Swanson design). Examination of 50 preoperative and postoperative radiographs revealed a decrease in the hallux abductus angle of 21.46 +/- 2.66 degrees, and the intermetatarsal angle of 6.40 +/- 0.67 degrees; both of these figures have a statistically significant probability value of 0.05 attached. The mean patient age at time of surgery was 61.31 years; the mean follow-up time was 5.01 months. A literature review of implant arthroplasty for correction of hallux abducto valgus deformity is also presented.

Aged↗
PubMed1983

Stimulation of prostaglandin production in rabbit ileal mucosa by bradykinin.

When rabbit ileal mucosa was incubated with exogenous [3H]arachidonic acid (AA), its major metabolites, identified by comigration with known standards on thin-layer chromatography, were prostaglandin (PG) E2, 6-keto-PGF1 alpha and to a lesser extent PGF2 alpha and PGD2. The rate of prostanoid release from the serosal surface of the mucosa only was increased after incubation th either bradykinin, lys-bradykinin, melittin or the calcium ionophore A 23187, in a rapid and dose-dependent fashion. Peptide concentrations as low as 10(-9) M were effective. Kinin-induced release of AA or its metabolites required the presence of Ca++ in the incubation medium. Stimulation of prostanoid release by lys-bradykinin was completely blocked by indomethacin. The combined lipoxygenase/cyclooxygenase inhibitors BW 755 and eicosa-5,8,11,14-tetraynoic acid and the lipoxygenase inhibitor nordihydroguaiaretic acid also blocked the stimulation of PG synthesis by lys-bradykinin. These inhibitors caused an increase in levels of AA released from the tissue by lys-bradykinin. The phospholipase inhibitors, mepacrine and U- 10029, inhibited the lys-bradykinin-stimulated release of both prostanoids and AA. At higher concentrations, U- 10029 inhibited the stimulation of transepithelial potential difference and short-circuit current across rabbit ileal mucosa produced by lys-bradykinin. These results support the hypothesis that bradykinin-stimulated intestinal secretion may be mediated by PGs.

Animals↗
PubMed1982

Early prenatal development of substance P and enkephalin-containing neurons in the rat.

The peroxidase-antiperoxidase (PAP) technique is used to determine the time of first detection and distribution of neuronal perikarya and processes showing substance P (SP)- and enkephalin (EN)-like immunoreactivity (LI) in the central and peripheral nervous system of the fetal rat. SPLI is first detected in central perikarya at E15. By E18, SPLI is less intensely localized in certain nuclei and shows heavier accumulations of immunoreactivity in central processes and in peripheral sensory neurons. ENLI is also widely distributed in perikarya and processes of the central nervous system at E18, but is not detected at E15. The distribution of SPLI and ENLI at E18 is comparable to that previously described in the adult brain with the following exceptions: (1) labeled perikarya and processes are not detected in the rostral forebrain; (2) axonal pathways are intensely labeled whereas most terminal fields are devoid of immunoreactivity.

Animals↗
PubMed1982

Enkephalin-containing neurons in substantia gelatinosa of spinal trigeminal complex: ultrastructure and synaptic interaction with primary sensory afferents.

The ultrastructural morphology and synaptic associations between enkephalin-containing neurons and sensory afferents was examined in the caudalis portion of rat spinal trigeminal complex, the region corresponding to Rexed's layer II of the dorsal horn. Specific antiserum to Met5-enkephalin was localized by the peroxidase-antiperoxidase technique in normal adult rats and in rats having electrolytic lesions of the trigeminal ganglia at 2, 4 and 6 days prior to sacrifice. In both normal and lesioned animals, the enkephalin-like immunoreactivity (ELI) was diffusely distributed throughout the cytoplasm of neuronal perikarya, dendrites, myelinated and unmyelinated axons, and axon terminals. The axons terminals were characterized by the presence of both small (40-60 nm) clear, and large (60-100 nm), dense-core vesicles and by the formation of predominantly axodendritic synapses. Optimal visualization of degenerating terminals occurred at 4 days after lesions of the trigeminal ganglia. Approximately one-third of the degenerating afferents were in either direct contact or were separated from an enkephalin-containing process by an intervening unlabeled dendrite. The occurrence of a well defined membrane density between a degenerating and enkephalin-labeled bouton was rare. Most commonly, the processes showing ELI were either unassociated or formed a triad arrangement with the degenerating afferents. Within the triad, the degenerating bouton formed a junction with an unlabeled dendrite which in turn was synaptically connected at the same level to an enkephalin-labeled process, usually a dendrite. We conclude that an intermediary neuron may be involved in interactions between primary sensory afferents and enkephalin-containing neurons in spinal trigeminal complex.

Animals↗
PubMed1982

Stimulation of colonic secretion by lipoxygenase metabolites of arachidonic acid.

Both 5-hydroperoxyeicosatetraenoic acid (5-HPETE) and 5-hydroxyeicosatetraenoic acid (5-HETE) increased the short-circuit current (Isc) in rabbit colonic mucosa mounted in vitro in Ussing chambers. Measurements of chlorine-36 fluxes indicated that the Isc response to 5-HPETE is due to stimulation of active chlorine secretion. 9-, 11-, and 12-HPETE's and leukotrienes C4 and B4 produced either very small increases in Isc or no increase. In contrast to results in rabbit colon, no HPETE, HETE, or leukotriene was effective in rabbit ileal mucosa. The effects of 5-HPETE in the rabbit colon were unaffected by mepacrine, but could be partially blocked by indomethacin. These results suggest that drugs which block both cyclooxygenase and lipoxygenase may be effective antidiarrheals in patients with colitis.

Animals↗
PubMed1982

Regulation of mast cell histamine release by neurotensin.

Neurotensin (NT), a neuropeptide found both centrally and peripherally, stimulated release of histamine from rat peritoneal mast cells in a dose-dependent manner. Release was evident by 10 nM and reached a plateau of 15-20% total cellular histamine by 10(-7)-10(-6) M NT. Optimal conditions for stimulation occurred at pH 6.5-7.5, 37 degrees C and at calcium concentrations of less than 1 mM. Release was complete within 2 minutes of peptide addition. Studies of histamine release by NT analogues indicted that the C-terminus is the biologically active portion of the molecule in this system, as is true of all other systems responsive to NT (1). D-Trp11-NT, which acts as a NT antagonist in several peripheral NT-sensitive tissues (2,3), also inhibited NT action on mast cells. Manipulations involving Ca2+ availability suggest that the mechanism of NT stimulation may involve use of intracellular Ca2+ to a greater extent than extracellular Ca2+. Lowering the extracellular Ca2+ concentration or blocking influx of extracellular Ca2+ with lanthanum (La3+), had little effect on NT-induced release, whereas Ca2+ depletion by treatment with ethylenediaminetetracetic acid (EDTA) or blockade of intracellular Ca2+ mobilization by N,N-(diethylamino)octyl 3,4,5-trimethoxybenzoate (TMB-8), inhibited the response to NT. Increasing cellular levels of adenosine 3',5'-cyclic monophosphate (cAMP), by treatment with 8-bromo-cAMP or stimulation with prostaglandin E2 (PGE2) in the presence of isobutylmethylxanthine (IBMX), served to reduce histamine release by NT, indicating that cAMP may play a role in NT stimulation.

Animals↗
PubMed1982

Cholinergic agonists induce vectorial release of serotonin from duodenal enterochromaffin cells.

Serotonin-containing enterochromaffin cells in the rabbit duodenal mucosa span the tissue contacting both the luminal and serosal sides. When the serosal surface is stimulated with carbachol in vitro, serotonin is secreted on the serosal side but not the mucosal side. Carbachol added to the luminal side is ineffective. Atropine but not hexamethonium blocks the effect of carbachol. Acetylcholine on the serosal surface also stimulates serotonin release on the serosal side. These findings indicate that enterochromaffin cells possess on their serosal surfaces muscarinic receptors that mediate vectorial release of serotonin when activated by cholinergic agonists.

Acetylcholine↗
PubMed1982

Characterization of the opiate receptor in the guinea-pig ileal mucosa.

Several opioid peptides and narcotic drugs reduced transepithelial potential difference (PD) and short circuit current (Isc) in guinea-pig ileal mucosa measured in vitro in Ussing chambers. [D-Ala2,D-Leu5]enkephalin was the most potent peptide tested. Enkephalin analogues with altered C-terminal amino acids were less potent, as were beta-endorphin and dermorphin. Etorphine produced potent effects whereas morphine and SKF 10,047 were inactive. Ethylketazocine produced a biphasic dose-response curve. When added by themselves diprenorphine and naloxone produced small increases in Isc. This effect was not seen when Cl- and HCO3- in the Ringer were replaced by SO42-. Diprenorphine and naloxone were able to shift the dose response curves for all agonists to the right, with the exception of that for ethylketazocine. Diprenorphine was a more potent antagonist than naloxone. SKF 10,047 also acted as a pure antagonist. Morphine and ethylketazocine had no antagonist effects. It is concluded that the opiate receptor in the guinea-pig ileal mucosa is similar to a delta-opiate receptor as defined by ligand binding studies, but that some differences also exist.

Animals↗
PubMed1982

Neurotensin.

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Animals↗
PubMed1982

alpha 2-Adrenergic receptor regulation of ion transport in rabbit ileum.

Catecholamines are known to decrease short-circuit current (Isc), stimulate NaCl absorption, and inhibit HCO3 secretion in rabbit ileal mucosa in vitro. These effects appear to be mediated by alpha-adrenergic receptors because they are partially blocked by phentolamine and not by propranolol. To further characterize this receptor system, we determined the interactions of epinephrine (Epi) with alpha-subtype-selective antagonists. Prazosin (PZ), a specific alpha 1-antagonist, did not alter the Epi dose-response curve at concentrations up to 10(-5) M. Yohimbine (YO), a specific alpha 2-antagonist, completely inhibited the Epi effect on Isc. At 10(-5) M, YO increased by 70-fold the concentration of Epi required to produce a half-maximal effect (ED50; from 1.4 X 10(-7) M to 10(-5) M). YO and PZ by themselves had no significant effect on Isc in concentrations up to 10(-5) M. Clonidine, a specific alpha 2-agonist, decreased Isc with an ED50 similar to that of Epi; its effect was blocked by YO but not by PZ. Two alpha 1-selective agonists, methoxamine and phenylephrine, only caused a decrease in Isc in doses greater than 10(-5) M. This effect was reversed by YO but not by PZ. The effects of YO and PZ on Epi-modified Cl fluxes were also determined. YO completely aborted the effects of Epi on net Cl flux. No significant effects were seen with PZ. We conclude that the effects of Epi on ileal ion transport are mediated by a specific alpha 2-adrenergic receptor present in ileal mucosa and that no physiologic alpha 1-receptor function can be demonstrated.

Animals↗