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Biomedical subjects

L Monti-Bloch

Publications and source records attributed to L Monti-Bloch.

At least 19 recordsLinked to original sources
PubMed2000

Behavioral and electrophysiological effects of androstadienone, a human pheromone.

Androstadienone is the most prominent androstene present on male human axillary hair and on the male axillary skin surface. We have previously shown that this volatile steroid is able to stimulate [corrected] the human female vomeronasal organ in picogram (pg) quantities, resulting in changes in autonomic activity. These effects are gender-specific. The purpose of the present study was to ascertain whether androstadienone could be considered a human pheromone by altering behavior as well as autonomic function. Forty normal female subjects were randomized in a double-blind manner to receive either control or 100 pg of androstadienone directly to the vomeronasal organ. We report that administration of this steroid under these conditions results in a significant reduction of nervousness, tension and other negative feeling states. Concordant changes were observed in autonomic physiology.

Adult↗
PubMed1998

The human vomeronasal system. A review.

Recent publications show that the human vomeronasal organ (VNO) develops and grows during gestation, and is present in all adult humans. The human VNO has a unique ultrastructure, with elongated bipolar microvillar cells that stain with several immunomarkers. These cells show physiological properties similar to chemosensory receptor cells of other mammalian species. The adult human VNO displays species-specific, gender-dimorphic and highly stereospecific responses to ligands. The organ's local response, or electrovomerogram, is followed by gender-specific behavioral changes, modulation of autonomic nervous system function, or the release of gonadotropins from the pituitary gland. Functional brain imaging studies revealed consistent activation of the hypothalamus, amygdala and cingulate gyrus-related structures during adult human VNO stimulation. These findings present new information supportive of a functional vomeronasal system in adult humans.

Adult↗
PubMed1998

Modulation of serum testosterone and autonomic function through stimulation of the male human vomeronasal organ (VNO) with pregna-4,20-diene-3,6-dione.

In mammals, external chemosensory signals from conspecifics of the opposite sex acting on vomeronasal organ receptors can modulate the release of gonadotropins. There is developmental, anatomical and functional evidence showing that the human vomeronasal organ (VNO) has the characteristics of a chemosensory organ. We have been using naturally occurring human pheromones to serve as models for designing novel synthetic compounds that we call vomeropherins. In previous publications we reported that vomeropherin pregna-4,20-diene-3,6-dione (PDD) delivered to the VNO of normal female and male human volunteers significantly affected male subjects only, decreasing respiration and cardiac frequency, augmenting alpha brain waves, and significantly decreasing serum luteinizing hormone (LH) and follicle stimulating hormone (FSH). Results of the present work confirm that PDD produces a local dose-dependent effect in the male human VNO. This is followed by a mild parasympathomimetic effect characterized by 10% increase of vagal tone, together with decreased frequency of electrodermal activity events. Furthermore, PDD locally delivered to the male human VNO significantly decreases serum LH and testosterone (p < 0.01). The present results contribute additional evidence supporting the functionality of the human VNO and its repercussions in autonomic and psychophysiological functions, as well as in neuroendocrine secretions.

Dose-Response Relationship, Drug↗
PubMed1996

The functionality of the human vomeronasal organ (VNO): evidence for steroid receptors.

The human vomeronasal organ (VNO) is an anatomical entity which is generally considered to be vestigial or non-functional. Nevertheless, a steroidal vomeropherin applied to the human VNO, results in changes of autonomic function, pulsatile release of luteinizing and follicle-stimulating hormones, autonomic and electroencepholographic activity. The vomeropherin pregna-4,20-diene-3,6-dione (PDD) was delivered as pulses in an air stream directed into the lumen of the VNO or to the surface of the olfactory epithelium and respiratory epithelium of the nasal septum. Single stimuli at a concentration of 10(-10) to 10(-8) M produced dose-dependent changes of the electrovomerogram. No significant effects were observed when the same applicator delivered identical stimuli to the nasal respiratory epithelium or to the olfactory epithelium. Administration of the vomeropherin to male subjects changed gonadotropin pulsatility. In males, PDD (5 x 10(9) M) decreased luteinizing hormone (LH) pulsatility which resulted in a statistically significant reduction of plasma LH levels (P < 0.009) and follicle-stimulating hormone (FSH) pulsatility (P < 0.021), but it produced no significant effects in female subjects. Prolactin (PRL) was not significantly affected by this vomeropherin in either male or female subjects. These data demonstrate, for the first time, the existence of a functional vomeronasal-pituitary pathway in adult humans. In addition to the effect on gonadotropin pulsatility, the vomeropherin also produces concurrent reflex autonomic effects after VNO stimulation. These included decreased respiratory frequency, increased cardiac frequency, and event-related changes of electrodermal activity and EEG pattern. Therefore, this investigation also provides evidence for functional connections between the VNO and a variety of hypothalamic areas in adult humans.

Administration, Intranasal↗
PubMed1994

The human vomeronasal system.

We studied the functional characteristics of the vomeronasal system in clinically normal adult subjects of both sexes (ages 20-45). Chemosensory substances were administered in punctate pulses in a continuous air stream from the tip of a multifunctional miniprobe, which contained a nonpolarizable electrode. Negative potentials with the characteristics of receptor potentials were recorded from the surface of the vomeronasal organ (VNO) and olfactory epithelium (OE) in response to certain substances defined here as vomeropherins (see definition in the introduction of the main text) and to olfactants. Stimulation of the VNO with femtomole amounts of vomeropherins produced a local depolarization with the characteristics of a receptor potential. The same substances produced only a small response from the OE, and no response from the nasal respiratory mucosa. Three vomeropherins PH15, PH78, and PH84 were particularly well recognized by the VNO of most male subjects (p < .01; n = 30). Substances PH30, PH56, and PH94B, produced similar effects in the VNO of most female subjects (p < .01; n = 30). Responses to virtually all vomeropherins exhibited a sexual dimorphism. Stimulation of the OE with the same quantity of odorants 1,8-cineole and l-carvone produced depolarization of 6.8 +/- 2.6 mV, but little or no response in the VNO. Therefore, the human VNO seems to have a unique specificity for certain chemosensory substances when compared to the OE. Administration of PH15 and PH78 to the VNO of male subjects (but not to female subjects) significantly increased electrodermal activity (p < .02) and skin temperature (p < .01). On the other hand, administration of PH84 to the VNO of male subjects decreased skin temperature but had little effect on electrodermal activity. Autonomic changes were accompanied by an increased percentage of alpha-cortical activity for all three vomeropherins. In female subjects (but not in male subjects) vomeropherins PH56 and PH94B significantly increased electrodermal activity (p < .01), skin temperature (p < .01), and alpha-cortical activity (p < .01). Local application of the olfactants 1,8-cineole and l-carvone to the VNO did not trigger autonomic responses or significant changes in the electroencephalographic pattern in male or in female subjects. Our studies indicate the adult human VNO is a functional chemosensory organ with a sexually dimorphic specificity and the ability to transduce signals which modulate certain autonomic parameters.

Adult↗
PubMed1993

Electrical communication between glomus cells of the rat carotid body.

Glomus cells of rat carotid bodies can be electrotonically coupled. This was determined by simultaneous intracellular recording and stimulation of two neighboring cells. Voltage applied into one cell (V1), was detected in the other cell as E2. The ratio E2/V1 or coupling coefficient (KC), varied from 0.003 to 1. R0 or input resistance (24.1-3,500 M omega), was calculated from the voltage elicited in the injected cell by current injection (V1/I1). The coupling resistance (RC) was estimated by using Bennett's model and was inversely related to KC. It ranged from 8.5 to 46,112 M omega. Values for KC are provisional since we may not have always recorded from immediately adjacent cells. Similarly, calculations of R0 and RC may not be accurate since, in all probability, there is a multicellular network. Stimulation by hypoxia (100% N2 or Na2S2O4), acidity (lactic acid or 100% CO2), dopamine, ACh, nicotine and bethanechol depolarized the majority of glomus cells, their input resistance decreased and cells became uncoupled. Fewer cells were either unaffected or coupling increased. There was a significant and negative correlation between changes in coupling coefficient and in coupling resistance.

Acetylcholine↗
PubMed1993

Effects of dopamine on type I chemoreceptor cells of the rat carotid body.

The effects of dopamine (DA) were studied on type I cells of the rat carotid body. DA (0.35 to 8.4 x 10(-4) M) elicited a long-lasting depolarization and decreased input resistance (Ro) in 75% of the cells, in a dose-dependent manner. Hyperpolarization and increased Ro were observed in 8% of cells. Membrane potential (Em) and Ro changes were highly correlated (-0.62, P < 0.001). The reversal potential (Erev) of the DA effect was +2.16 +/- 4.75 (mV +/- S.E.M.).

Animals↗
PubMed1993

Vomeronasal epithelial cells of the adult human express neuron-specific molecules.

Immunohistochemical localization of three molecular markers, neuron-specific enolase (NSE) and protein gene product (PGP) 9.5 for neurons and neuroendocrine cells, and olfactory marker protein (OMP) for olfactory receptor neurons (ORNs) was investigated in the vomeronasal epithelium (VNE) of adult humans. NSE- and PGP 9.5-immunoreactive cells were identified in the VNE. ORNs in the olfactory epithelium of approximately age-matched controls were immunoreactive for the three markers. Most NSE-immunoreactive cells in the VNE were bipolar and similar in shape to the NSE- and PGP 9.5-immunoreactive ORNs. The results indicate that the adult human VNE contains cells expressing two molecular markers characteristic of neurons and that these cells bear a striking morphological similarity to ORNs.

Adult↗
PubMed1991

Ultrastructure of the human vomeronasal organ.

Virtually all vertebrates have a vomeronasal system whose involvement in pheromone detection plays a crucial role in reproduction. In humans, the vomeronasal organ has been assumed to be vestigial or absent and without functional significance. In the present study involving over 400 subjects, vomeronasal pits were observed in all individuals except those with pathological conditions affecting the septum. Electron microscopy of the adult human vomeronasal organ indicates the presence of two potential receptor elements in the pseudostratified epithelial lining: microvillar cells, and unmyelinated, intraepithelial axons. In addition, unmyelinated axons are common in the lamina propria surrounding the organ. They appear to constitute the components essential for a functional chemosensory system, and may thus provide the basis for a pheromone detection system as in other animals.

Adult↗
PubMed1991

Effect of putative pheromones on the electrical activity of the human vomeronasal organ and olfactory epithelium.

The summated receptor potential was recorded from the vomeronasal organ (VNO) and olfactory epithelium (OE) of 49 human subjects of both sexes (18 to 55 years old) using surface non-polarizable silver-silver chloride electrodes. 15-25 pg of human putative pheromones, clove oil and a diluent were administered to the VNO or the OE in 0.3-1 s pulses from a 0.05 mm dia cannula connected to a multichannel delivery system. Local stimulation of the VNO produces negative potentials of 1.8-11.6 mV showing adaptation. Responses are not obtained when the recording electrode is placed in the nasal respiratory mucosa. Pheromone ER-830 significantly stimulates the male VNO (P less than 0.01; n = 20), while ER-670 produces a significant effect on female subjects (P less than 0.001; n = 20). The other pheromones tested do not show significantly different effects in both male and female (P greater than 0.1). Similar quantities of odorant or diluent produce an insignificant effect on the VNO. Stimulation of the OE with clove oil produces depolarization of 12.3 +/- 3.9 mV, while pheromones do not show a significant effect. Our results show that the VNO is a functional organ in adult humans having receptor sites for human putative pheromones.

Adolescent↗
PubMed1990

Effects of denervation on the glomus cell membrane.

Trophic influences of the carotid nerve (CN) on carotid body (CB) glomus cells were studied by comparing the membrane potential (Em), input resistance (Ro) and voltage noise (Erms) of normal and 3-31-day denervated cells had more negative Ems. Higher Ros were recorded at 3 and 6 days. Erms sharply increased at 3 days, returned to normal at 6-15 days and was below normal at 31 days. A transmitter (ACh) and NaCN, producing histotoxic anoxia, were used for stimulation. These substances either depolarized or hyperpolarized innervated cells and increased or decreased voltage noise. Denervation selectively changed these patterns but only for a short time. ACh preferentially depolarized the cells, only at 3 days, whereas its effects on noise did not change. The Em responses to NaCN remained unaltered although at 3-6 days noise increases were smaller and depressions exaggerated. Possible reasons for these effects are discussed.

Acetylcholine↗
PubMed1989

Changes in glomus cell membrane properties in response to stimulants and depressants of carotid nerve discharge.

Intracellular recordings were made from glomus cells in the excised, intact or sliced (150-200 microns) carotid body. Carotid nerve discharge was also recorded from intact preparations. Slices were prepared for visual (Nomarski) control of microelectrode impalement. Resting potential (Em), input resistance (Ro) and voltage noise (Erms) were measured in control conditions and in response to several stimulants (interruption of flow, hypoxic and histotoxic [NaCN]anoxia, hypercapnia, asphyxia and acidity) and depressants (alkalinity, cooling) of the carotid nerve sensory discharge. Different glomus cells responded differently to the same stimulus but significant trends were found. The more common responses to zero flow and anoxia (hypoxic and histotoxic) were depolarization (64%) and decreases in Erms (63%) and Ro (71%). When extracellular pH was varied from 8.5 to 5.0, the preponderant responses were cell depolarization, and increases in noise and input resistance as pH decreased. Consequently, cell depolarization induced by zero flow and anoxia tended to be accompanied by reduced Ro, whereas that induced by acidity generally showed increased Ro. Changes in voltage noise usually followed variations in Ro. When nerve discharge frequency was plotted against delta Em or delta Erms there were positive correlations during acid stimulation. However, these correlations were complex (parabolic) during flow interruption and anoxia: an increase in discharge occurred in response to cell depolarization and to hyperpolarization. These results suggest that hypoxia and hypercapnic or acidic stimuli act on glomus cells by different mechanisms. This finding is consistent with evidence obtained by recording carotid nerve discharges in intact animals.

Animals↗
PubMed1985

Effects of methionine-enkephalin and substance P on the chemosensory discharge of the cat carotid body.

The effects of methionine enkephalin (ME) and substance P (SP) were tested on the chemosensory discharge of the cat carotid body-nerve preparation in vitro. ME superfused in concentrations of 10(-8) to 10(-5) M depressed the sensory discharge, an effect followed by receptor excitation (rebound). Bolus applications of ME (30 ng to 3.0 microgram) induced variable effects (excitation or depression) on the discharge, excitation being more pronounced with the smaller doses. Superfusions with SP (10(-8) to 10(-5) M) either excited or depressed the discharge, excitation being more pronounced with higher SP concentrations (i.e. 10(-6) M). Bolus applications of SP (43 ng to 0.5 micrograms) also excited or depressed the sensory discharge. These variations may be dose-dependent. Superfused ME (10(-6) M) significantly depressed the chemoreceptor response to hypoxia (100% N2) and hypercapnia (6% CO2, pH 7.43). The responses to NaCN and acidity (pH 6.0) were marginally depressed. Superfused SP (10(-6) M) clearly depressed the responses to hypoxia, those to hypercapnia and NaCN were marginally affected but the effects of acidity were not altered. When the peptides were tested against the receptor responses to exogenously applied putative neurotransmitters (ACh, dopamine--DA), it was found that ME tended to depress both the ACh and DA actions whereas SP (10(-6) M) tended to increase their effects. Superfusions with naloxone (10(-6) M) increased the basal chemosensory discharge and this enkephalin blocker partially relieved the depressant effect of ME on the ACh-induced response. It is concluded that carotid body chemoreceptors have excitatory and inhibitory reactive sites to both ME and SP although their precise location is still unknown.

Acetylcholine↗
PubMed1983

Effects of temperature on denervated carotid body (glomus) cells.

Cat carotid bodies were denervated for 3-31 days by sectioning the carotid nerve. The normal response of glomus cells to cooling by about 6 degrees C, namely, membrane depolarization and reduced input resistance (Ro) was altered. At 3 days, cooling induced normal depolarization although Ro decreased more markedly. At 7 days, cooling depolarized 53% of the cells which was accompanied by variable Ro changes. Forty-seven percent of the cells were hyperpolarized and their Ro increased. At 16 days, a fall in temperature depolarized 25% of the cells which showed variable changes in Ro, whereas the rest showed hyperpolarization and increased Ro. At 31 days, cooling weakly depolarized 64% of the cells together with a small reduction in Ro whereas 28% showed some hyperpolarization and larger Ro. It is concluded that sensory denervation alters the membrane of glomus cells, the preneuronal component of the receptor complex.

Animals↗
PubMed1983

Effects of ischemia on the function and structure of the cat carotid body.

Interrupting the blood supply to the carotid body by ligating arteries of its vascular peduncle altered the chemoreceptive properties of the carotid nerve and produced structural changes in parenchymal (glomus and sustentacular) cells. The onset of ischemia was marked by an increase in the discharge of both A (myelinated) and C (unmyelinated) sensory fibers followed by depression and finally by receptor silence. The discharge of A-fibers disappeared after 30-50 min and that of C-fibers after 60-90 min. During ischemia of 15-60 min duration the threshold to pharmacological (NaCN, ACh) and 'natural' (hypoxic) stimuli progressively increased and was accompanied by reversible changes in the structure of parenchymal cells and nerve endings. Ischemia for 2 h or longer produced irreversible functional damage and disappearance of glomus and sustentacular cells from the carotid body. Following ischemic injury, nerve fibers regenerated and all responded to mechanical stimuli but only a few were stimulated by natural or pharmacological agents. Thus, parenchymal cells of the carotid body appear to be most important in transduction by allowing sensory fibers to respond to chemical stimuli.

Acetylcholine↗
PubMed1983

Carotid body grafts induce chemosensitivity in muscle nerve fibers of the cat.

The ability of carotid body parenchymal cells to change the physiological properties of nerve fibers was tested in 8 cats by transplanting the carotid body to the tenuissimus muscle and reinnervating the organ with the muscle nerve. Ninety-five to 174 days after the transplant, electrophysiological recordings were obtained from the reinnervating tenuissimus nerves. Forty percent of the regenerating nerve fibers having spontaneous activity responded to muscle stretch, hypoxia, NaCN, ACh, nicotine and dopamine, apparently because of dual innervation of glomus cells and muscle spindles. Five of 6 transplants, examined electron microscopically, contained viable glomus cells innervated by axon terminals. Neither the normal tenuissimus nerve nor the same nerve regenerating into adipose tissue grafts or to one non-viable carotid body transplant showed chemosensory properties although these grafts contained numerous, small myelinated axons indicative of extensive nerve regeneration. It is concluded that carotid body cells are capable of inducing chemosensory properties in axons that, normally, subserve a mechanosensory function.

Animals↗
PubMed1982

Nicotinic and muscarinic reactive sites in mammalian glomus cells.

Nicotinic and muscarinic sites on glomus cell membranes of cats, rabbits and mice were determined in carotid body slices. Cells were impaled under Nomarski optics. Resting potentials were 11.1-73.1 mV and input resistances were 11-250 M omega. Nicotine, pilocarpine or bethanechol depolarized glomus cells and their input resistance decreased. Curare or alpha-bungarotoxin reduced nicotine effects. Atropine had similar effects on the responses to pilocarpine or bethanechol.

Acetylcholine↗