Brain neurotransmitters and the development and maintenance of experimental hypertension

Buccafusco, Jerry J.; Brezenoff, Henry E.

doi:10.1007/978-3-0348-9311-4_4

Cited by 13 publications

(5 citation statements)

References 81 publications

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“…Buccafusco's graduate training in pharmacology, his postdoctoral work, and the early years of his academic career focused on the role of cholinergic neurons in the central nervous system's regulation of the cardiovascular system. This seminal work contributed to our understanding of how cholinergic neurons in the brain (particularity the brain stem) influence blood pressure as well as how several antihypertensive agents (e.g., clonidine, methyldopa) act on central cholinergic neurons either directly or indirectly to decrease blood pressure [1] and [2]. Later his focus shifted to studying the means to prevent or reverse the acute toxicity associated with the most toxic forms of cholinesterase inhibitors – the chemical nerve agents such as soman and sarin.…”

Section: Introductionmentioning

confidence: 99%

Neurobiology of nAChRs and cognition: A mini review of Dr. Jerry J. Buccafusco's contributions over a 25 year career

Terry

Decker

2011

Biochemical Pharmacology

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This review highlights some of the many contributions of the late Dr. Jerry J. Buccafusco to the neurobiology of nicotinic acetylcholine receptors (nAChRs) and cognition over a 25 year period. The article is written by two of Dr. Buccafusco's professional colleagues, one from academia and one from the pharmaceutical industry. While Dr. Buccafusco's expertise in the cholinergic field was extensive, his insights into the practical relevance of his work (with a long-term goal of formulating new drug development strategies) were unique, and a great asset to both the basic science community and pharmaceutical companies. In 1988, Dr. Buccafusco's laboratory was the first to report the cognitive enhancing action of low doses of nicotine in non-human primates. Since that time he studied a large number of novel pro-cognitive agents from several pharmacological classes in rodents as well as monkeys. Based on years of observing paradoxical effects of nicotinic ligands in vitro and in vivo, Dr. Buccafusco made the provocative argument that it might be possible to develop new chemical entities (with pro-cognitive actions) that have the ability to desensitize nAChRs without producing an antecedent agonist action. Some of his more recent work focused on development of single molecular entities that act on multiple CNS targets (including nAChRs) to enhance cognition, provide neuroprotection, and/or provide additional therapeutic actions (e.g., antipsychotic effects). Dr. Buccafusco's influence will live on in the work of the numerous graduate students, postdoctoral fellows, and junior faculty that he mentored over the years who now serve in prestigious positions throughout the world.

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Section: Introductionmentioning

confidence: 99%

Neurobiology of nAChRs and cognition: A mini review of Dr. Jerry J. Buccafusco's contributions over a 25 year career

Terry

Decker

2011

Biochemical Pharmacology

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“…This phenomenon can be readily demonstrated by the marked pressor responses observed in several animal species, including humans, after the administration of centrally-acting cholinergic (muscarinic) agonists (for review, see Brezenoff and Giuliano, 1982;Buccafusco and Brezenoff, 1986;Buccafusco, 1992Buccafusco, , 1996. Central cholinergic neurons also have been reported to participate in mediating the pressor action to central administration of nicotine (Buccafusco and Yang, 1993), and certain noncholinergic neurotransmitter substances such as angioArticle, publication date, and citation information can be found at…”

Section: Introductionmentioning

confidence: 99%

The Importance of Brainstem Cholinergic Neurons in the Pressor Response to Cocaine

Buccafusco¹,

Davis²,

Shuster³

et al. 2004

J Pharmacol Exp Ther

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After intracisternal injection, 140 nmol (48 g) of cocaine (but not lidocaine or procaine) evoked an increase in mean arterial pressure (MAP) of 41 mm Hg. The increase in MAP began within 1 min after injection and lasted 10 to 15 min. The pressor response to intracisternal injection of cocaine was not mediated through central ␣-adrenergic receptors, but intracisternal pretreatment with D1 or D2 dopamine receptor antagonists shortened the duration of the response. Pretreatment with intracisternal injection of hemicholinium-3 to deplete medullary acetylcholine produced a dose-dependent inhibition of the pressor and tachycardic responses to intracisternal injection of cocaine. Central pretreatment with hemicholinium-3 also inhibited the pressor response to intravenous injection of 0.5 mg/kg cocaine. Atropine pretreatment was only partly effective in blocking the pressor and tachycardic responses to intracisternal injection of cocaine. However, a single intracisternal injection of the nicotinic ganglionic receptor blocker hexamethonium inhibited the pressor response to cocaine administered intracisternally 24 h later, and on each of the following 4 days. The blocking effect of hexamethonium was not mimicked by the ␣7 selective antagonist methyllycaconitine or by the ␣4␤2 subtype-preferring antagonist dihydro-␤-erythroidine. The data suggest that the pressor response to cocaine is mediated by medullary acetylcholine release on to nicotinic receptors of the ganglionic type, enhancing the output of bulbospinal sympathetic premotor neurons. Our results provide new evidence for the prolonged inactivation of relevant central nicotinic receptors by nicotinic receptor antagonists, and suggest that such compounds might be used safely for cocaine overdose, as well as for antiabuse issues without the concern for autonomic side effects.The ability of cocaine to increase systemic blood pressure usually is considered to be commensurate with drug's pharmacological classification as an indirect-acting sympathomimetic amine. Whereas cocaine conforms to this classification both in the peripheral and central nervous systems, the role of the CNS in terms of blood pressure alterations has been debated (Knuepfer et al., 1993;Gillis et al., 1995;Bernards, 1996). In fact, agonists at central ␣ 2 -adrenergic receptors such as clonidine and ␣-methyldopa are effective antihypertensive drugs; and levodopa and other dopaminergic antiParkinson agents often produce orthostatic hypotension as a side effect. Also, systemic administration of cocaine has been reported to decrease sympathetic nervous activity (Knuepfer and Branch, 1992;Gillis et al., 1995;Abrahams et al., 1996). Yet, there have been instances when cocaine has been administered directly into the CNS, usually via the cerebrospinal fluid, that the drug elicits an increase in arterial blood pressure. However, based upon the requirement for relatively high doses to elicit a pressor response via the lateral ventricular route (Knuepfer et al., 1993), it is unlikely that forebrain str...

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“…Studies in this and several other laboratories have pointed to the critical role of central cholinergic neurons in cardiovascular regulation. Drugs that activate central muscarinic receptors or enhance neuronally released acetylcholine can elicit a reproducible and significant increase in arterial blood pressure in animals and man (for review, see Brezenoff and Giuliano, 1982;Buccafusco and Brezenoff, 1986). One animal model, the spontaneously hypertensive rat (SHR), exhibits an exaggerated pressor response to central cholinergic stimulation (see Makari et al, 1989), an effect which may be due to heightened central cholinergx activity (Buccafusco and Spector, 1980;Trimarchi and Buccafusco, 1987).…”

Section: Introductionmentioning

confidence: 99%

The effect of the acetylcholine transport blocker vesamicol on central cholinergic pressor neurons

Buccafusco

Wei

Kraft

1991

Synapse

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Vesamicol (AH5183) inhibits the uptake of acetylcholine into cholinergic neuronal storage vesicles. Earlier in vitro studies have demonstrated that such inhibition can lead to a failure of transmission, particularly in peripheral cholinergic tissues. The present study was designed to determine whether vesamicol could inhibit central cholinergic transmission in conscious freely moving rats. Central (lateral cerebroventricular) injection of 20 micrograms of vesamicol significantly reduced the hypertensive and bradycardic response to subsequent central injection of physostigmine in spontaneously hypertensive rats. Inhibition of the pressor response was greatest when physostigmine was administered 1 hr after vesamicol. Acetylcholine and choline levels were determined in three brain regions derived from rats treated one hr earlier with either vehicle or vesamicol. Acetylcholine levels were found to be unaltered after vesamicol treatment, although choline levels were significantly higher in two brain regions. These results are consistent with the ability of vesamicol to inhibit the function of central cholinergic cardiovascular regulatory neurons. The mechanism for this inhibition is not related to depletion of total brain acetylcholine content but may be due to depletion of a small critical pool of transmitter.

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Brain neurotransmitters and the development and maintenance of experimental hypertension

Cited by 13 publications

References 81 publications

Neurobiology of nAChRs and cognition: A mini review of Dr. Jerry J. Buccafusco's contributions over a 25 year career

Neurobiology of nAChRs and cognition: A mini review of Dr. Jerry J. Buccafusco's contributions over a 25 year career

The Importance of Brainstem Cholinergic Neurons in the Pressor Response to Cocaine

The effect of the acetylcholine transport blocker vesamicol on central cholinergic pressor neurons

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